Comparisons of human immunodeficiency virus (HIV) disease progression between risk groups are difficult primarily because of the long incubation period of acquired immune deficiency syndrome (AIDS) and unknown times of infection. This is believed to be the first study that directly compared changes in T-lymphocyte subsets following HIV-1 seroconversion between cohorts of predominantly black injecting drug users and predominantly white homosexual men. Longitudinal trends of CD4 and CD8 percentages of total lymphocytes during 4 years were modeled as piecewise linear functions with a two-parameter correlation structure to accommodate within-person repeated observations. Prior to seroconversion the 151 injecting drug users started with similar CD4% and CD8% levels compared with the 99 homosexual men. Following seroconversion, larger changes were observed overall in the homosexual men compared with the injecting drug users for both markers (p < or = 0.001). The major discrepancies, however, were limited to the first 2 years. Subsequently, the CD4% levels of the two cohorts converged and then declined at similar rates. These comparative analyses of HIV seroconverters in homosexual men and injecting drug users suggest that risk group has only a minor effect on the initial course of HIV infection.