Serum cytokine levels and peripheral T cell subpopulations of HIV-1-infected patients before, during and after active visceral leishmaniasis (VL) were analysed and compared with appropriate controls. At VL diagnosis, co-infected patients showed higher serum levels of interferon-gamma (IFN-gamma) than matched HIV-1 controls without VL, and lower serum concentrations of IL-10 than non-immunocompromised VL controls. High levels of tumour necrosis factor-alpha (TNF-alpha) and IFN-gamma were present in the sera of HIV-1-infected patients with active VL. TNF-alpha remained elevated after VL recovery. A steady decline in the CD4+ cell count, an increase of serum HIV viraemia and a progressive seroconversion for the HIV-1 p24 antigen was observed during the course of VL disease. Thus, an aberrant activation of the TNF system with possible negative immunological and virological consequences is present in HIV-1-infected patients with VL. A more extensive prospective validation of these findings in a bigger cohort of patients will nevertheless be necessary. The results support the hypothesis that different opportunistic infection agents may trigger the production of proinflammatory cytokines during immunodeficiency, and in this way accelerate the course of HIV-1 disease.