Objective: The concentration of type 1 and type 2 cytokines and fibroblast‐associated apoptosis‐1 soluble receptor (sAPO‐1/Fas) was analysed in the sera of Ugandan and Italian HIV‐1‐seropositive and seronegative individualls. The data were compared to determine whether the immunological status of these groups was different. Methods: Sixty‐seven Ugandan and 30 Italian HIV‐positive patients were analysed and stratified according to CD4 counts (group 1, > 500×106/l; group 2, 200–500×106/l; group 3, < 200×106/l). Sera from 15 Ugandan and 11 Italian HIV‐negative blood donors were also analysed. Serum concentration of type 1 cytokines [interleu‐kin (IL)‐2, IL‐12, and interferon (IFN)‐&ggr;] and type 2 cytokines (IL‐4 and IL‐10), and sAPO‐1/Fas were measured by enzyme‐linked immunosorbent assay. Results: Serum levels of IL‐2, IFN‐&ggr; and IL‐10, but not of IL‐4 and IL‐12, were elevated in HIV‐positive group 1 and 2 Africans compared with HIV‐positive Italian individuals. IL‐4 was mildly augmented in HIV‐positive group 3 African patients. Serum concentration of sAPO‐1/Fas was reduced in HIV‐positive Africans compared with HIV‐positive Italian individuals. Finally, serum levels of IL‐2 and IL‐10 were increased and sAPO‐1/Fas reduced when sera of HIV‐negative African healthy controls were compared with their Italian counterparts. The ratio of type 1/type 2 cytokines was roughly 1.0 in HIV‐negative African controls, and much greater than 1.0 in HIV‐negative Italian controls. Conclusions: These preliminary findings indicate that immune activation is present in African HIV infection. Furthermore, these data raise the possibility that abnormal immune activation and increased susceptibility to antigen‐induced cell death is present even in HIV‐negative African controls.