The late effects of chemotherapy on immunologic parameters in AIDS-related non-Hodgkin lymphoma (NHL) have not been described. From a cohort of 105 consecutive patients treated with infusional chemotherapy and highly active antiretroviral therapy (HAART), 68 survived more than 3 months following the end of chemotherapy. Their lymphocyte subsets and plasma HIV viral loads were measured at regular intervals for 2 years and values compared with baseline. During chemotherapy, there were statistically significant falls in CD4 (helper T), CD8 (cytotoxic T), and CD19 (B) cell populations but no changes in the CD56 (natural killer [NK]) cell population. Among the 68 survivors, there were statistically significant increases in CD4, CD8, CD19, and CD56 cell populations during the first year of follow up, compared with the values at the start of chemotherapy. During the second year of follow up, there were further statistically significant rises in CD4 and CD19 cell populations, compared with the values at 12 months after chemotherapy. During 244 years of follow-up since chemotherapy in these 68 survivors, 7 second primary tumors and 8 opportunistic infections were diagnosed. Chemotherapy and concomitant HAART for AIDS-related NHL does not cause prolonged suppression of lymphocyte subsets. These data should provide reassurance regarding the long-term consequences of chemotherapy in these individuals.