Serum cytokine levels and mononuclear cell subpopulations in the spleen and peripheral blood of patients with visceral leishmaniasis before and after antimony therapy were analyzed. The percentages of activated monocytes/macrophages, T cells, and possibly B cells; of gamma/delta T cell receptor (TCR)-bearing T cells; of CD4- CD8- alpha/beta TCR-bearing T cells; and serum levels of tumor necrosis factor-alpha (TNF alpha), interferon-gamma (IFN-gamma), and interleukin-6 (IL-6) were high in patients with active visceral leishmaniasis. The proportion of both helper and suppressor CD4+ cells and of cells with NK and cytotoxic T phenotypes were depressed. Successful chemotherapy normalized these parameters with the exception of activated monocytes. Thus, the impaired cell-mediated immunity in human Leishmania donovani infection is primarily due to a decrease in the proportion and possibly the activity of helper CD4+ cells, while suppressor cells do not seem to play a relevant role. TNF alpha, IL-6, and IFN-gamma may prove to be useful markers for monitoring response to therapy.