Rabbit anti-dog lymphocyte serum plus rabbit complement had a rapid cytocidal effect on blood lymphocytes from 11 patients with chronic lymphocytic leukemia. The titer of the immune sera varied from 1:42 to 1:530 with a mean titer of 1:100. The sera showed minimal or no toxicity to lymphocytes from normal persons with a titer of > 1:10 in 13 of 18 cases. A similar differential toxicity to normal and leukemic lymphocytes was observed with rat anti-dog lymphocyte serum. However, guinea pig and horse anti-dog lymphocyte sera or globulin were equally toxic to normal and leukemic human lymphocytes. Leukemic lymphocytes incubated with rabbit anti-dog lymphocyte serum and rabbit complement showed early nuclear degenerative changes and paranuclear vacuoles. The cytologic degenerative changes suggested that the nucleus or nuclear membrane may be the first site of action of the immune serum.