During the final years of his house-officership, Coons joined the Thorndike Memorial Laboratory and was given a fellowship position in bacteriology and immunology.

[2] In 1942, Coons's research was interrupted by a call to serve in the Medical Corps of the United States Army during World War II.

Returning to Harvard Medical School, Coons continued his work on immunohistochemistry, in collaboration with Louis Fieser—an organic chemist—and his colleagues.

[3] In addition, the organisms were brightly fluorescent and could be seen easily with a microscope that was fitted with an excitational ultraviolet light source.

This basic laboratory paradigm was later applied to many antigens and antibodies,[4][5][6][7][8] launching the clinical disciplines of diagnostic immunofluorescence microscopy for bacteriology and immunology, immunocytology, and immunohistochemistry in anatomic pathology.

Coons progressed through the academic ranks at Harvard Medical School, and in 1953 was appointed Career Investigator for the American Heart Association.

[13] Despite those accolades, Coons remained a modest, affable, and quiet person who was devoted to his work, family, friends, and students.

Coons died of coronary artery disease and congestive heart failure in September, 1978, in Brookline, Massachusetts.

Coons was survived by his wife, Phyllis (née Watts) [1917-2002], a writer for the Boston Globe newspaper;[14] his son, Albert H., Jr. (1957–2003),[15] a Boston attorney; and four daughters: Elizabeth, a medical editor; Susan, an educator; Hilary, a clinical psychologist; and Wendy, a social worker.