Objective: To investigate the relationship between cytokine serum levels, peripheral blood lymphocyte subsets and clinical picture in acute primary HIV-1 infection. Patients and methods: Absolute number/μl total lymphocytes, CD4+, CD8+ and natural killer (NK) cells, as well as serum levels of soluble CD8 receptor, interleukin (IL)-1β, IL-2, lL-4, IL-6, tumour necrosis factor (TNF)-α, interferon (IFN)-γ, β2-microglobulin and 5′-neopterin were determined in 15 patients with acute primary HIV-1 infection, 16 asymptomatic HIV-1-seropositive individuals and 18 HIV-1-seronegative individuals at risk for HIV-1 infection. Results: Acute primary HIV-1 infection was characterized by significant CD4+ lymphocytopenia with low IL-2 serum concentrations, and by high absolute number of circulating CD8+ and NK cells, with elevated serum levels of soluble CD8 receptor, IL-1β, IFN-γ and 5′-neopterin. Follow-up of acute seroconverters showed a significant decrease in NK cell counts and 1L-1β levels, with an increase of IL-6. Conclusions: In acute primary HIV-1 infection, significant alteration of cytokine release, possibly induced by viral antigens, could be responsible for both clinical picture and activation of cytotoxic cells through abnormal mechanisms.