In 2000, with Owen Grabo having left the band, Twothirtyeight recorded their next EP, Matter Has a Breaking Point, as a three-piece outfit with Chris Staples on bass guitar and lead vocals.
With the addition of Jake Brown, former frontman of the band Driven, on bass guitar, Twothirtyeight wrote and recorded their second full-length album Regulate the Chemicals.
Chris Carrabba, notable as the former lead vocalist of Further Seems Forever and principal artist of Dashboard Confessional, contributed backing vocals to two of the songs from Regulate the Chemicals, "This Town Will Eat You" and "Coin Laundry Loser."
Lead vocalist Chris Staples went on to front the indie rock band Discover America and embarked on a solo career.
On April 17, 2012, Chris Staples announced via his official Facebook page that Twothirtyeight would be reuniting to play the Deluna Festival in Pensacola, Florida, which took place September 21 to 23, 2012.