This study investigated the effects of a combination antiretroviral drug regimen (indinavir and two nucleoside analogs or ritonavir and saquinavir) on the levels of CD34(+) colony-forming units (CFU-Cs) in the peripheral blood of HIV-1(+) patients, Ten patients who were receiving combination antiretroviral drug therapy were studied and their peripheral blood CD34+ CFU-Cs were measured prior to, 1 month after, and 4 to 6 months after the commencement of therapy, The levels of CD4(+) T cells increased significantly in these patients (paired t test, p = 0.0027) and plasma viral load became undetectable in all but one patient studied. Measurements of the CFU-Cs showed that their levels tended to increase on the commencement of therapy, nd these levels became significantly higher than baseline by 4-6 months (paired t test, p = 0.0293), Analysis of the different colony phenotype demonstrated that the main contributor to this increase consisted of burst-forming unit erythroid (BFU-E) cells, These data also demonstrated that there was an inverse correlation between the rise in CFU-Cs at 4-6 months compared with CD4(+) cell, CD8(+) cell, and neutrophil counts, and hemoglobin concentration, at baseline. The demonstrated increase in the levels of CD34(+) CFU-Cs suggests that HIV-1 may have an inhibitory effect on these cells in vivo, and that this inhibition may be abrogated by suppression of viral replication.