[2] McKernan grew up heavily influenced by African-American music, particularly the blues, and enjoyed listening to his father's collection of records and taught himself how to play harmonica and piano.

Unlike the other members of the Grateful Dead, McKernan avoided psychedelic drugs, preferring to drink alcohol (namely whiskey and flavored fortified wine).

[1] He came from Irish ancestry, and his father, Phil McKernan, was an R&B and blues disc jockey, who has been reported to have been one of the first white DJs on KDIA (later renamed KMKY), then a black radio station, by several sources.

[4] Onomastician Adrian Room has suggested McKernan was given the name due to his untidy and unclean habits[10] and band biographies say he got the nickname owing to his similarity to Pig-Pen, the permanently-dirty character in the comic-strip Peanuts.

[11] Along with Garcia and second guitarist Bob Weir, McKernan was a participant in the predecessor groups leading to the formation of the Grateful Dead, beginning with the Zodiacs and Mother McCree's Uptown Jug Champions.

He played an instrument on two tracks only (Hammond organ on "Black Peter" and harmonica on "Easy Wind", on which he also sang lead) on Workingman's Dead (1970), the band's breakthrough studio release.

On the follow-up album American Beauty, keyboard parts were handled by Garcia and Lesh, along with session musicians Howard Wales and Ned Lagin.

The 1971 live album Grateful Dead featured three overdubbed organ parts from Merl Saunders in addition to McKernan's contributions on "Big Railroad Blues", "The Other One", and "Me & Bobby McGee".

He began to alternate between the Vox Continental and the Hammond B-3 in June 1967, usually reserving the former instrument for outdoor and impromptu concerts, including the band's performance at the Columbia University protests of 1968.

[29] During Tom Constanten's tenure with the group, McKernan occasionally played his bandmate's double-manual Vox Super Continental on some songs (most notably "Death Don't Have No Mercy") through May 1969.

[29] McKernan sang lead on several standards he wanted the Dead to record, such as Otis Redding's "Pain in My Heart" and Wilson Pickett's "In the Midnight Hour", with the latter serving as one of the band's main improvisatory vehicles from 1966 to 1968.

[31][32] Unlike fellow vocalists Garcia and Weir, he sang lead without playing any instrument except harmonica and actively interacted with the audience, occasionally walking out into the crowd.

[33] McKernan achieved a new prominence in 1969 singing "Turn On Your Love Light"; initially introduced in 1967, the song gradually evolved into the band's show-stopping finale, often taking fifteen to thirty minutes to complete.

[34][35] When the Grateful Dead appeared at Woodstock, the band's set (which was marred by technical problems and general chaos and described as one of their worst shows) ended with "Turn On Your Love Light".

[36] Even as his instrumental contributions waned, McKernan's vocal performances remained an integral part of the band's live set; by early 1971, their cover of the Rascals' "Good Lovin'" (initially performed by the group as early as 1966 and featured at shows at the Fillmore East later released as Ladies and Gentlemen... the Grateful Dead) began to emerge as a secondary showcase of his improvisatory talents alongside "Love Light".

[39] Several new songs emerged from a creatively fecund period coinciding with his health problems in 1971, most notably "Mr. Charlie", a collaboration with Dead lyricist Robert Hunter.

[41] McKernan was close friends with American singer-songwriter Janis Joplin due to common musical influences and lifestyles, particularly a shared love of alcohol over other drugs;[42] a poster from the early 1970s showed them together at 710 Ashbury Street, the Grateful Dead's communal home from 1966 to 1968.

[43][44] Joplin joined McKernan on stage at the Fillmore West on June 7, 1969, with the Grateful Dead to sing his signature "Turn On Your Love Light",[45] reprising this duet on July 16, 1970, at the Euphoria Ballroom in San Rafael, California.

Although manager Rock Scully alleged that McKernan passed out in front of his Hammond organ at one show during this period, Garcia biographer Blair Jackson has lauded the quality and frequency of his instrumental contributions on the Europe '72 tour.

He took over de facto frontman duties in concert and began to reintroduce material originally chosen by McKernan into the Dead's live set after his death.

[66] Jimmy Reed's "Big Boss Man", recorded by the group on Grateful Dead (Skull and Roses) with McKernan singing lead, was revived by Garcia and performed occasionally through the 1980s and 90s.