Serum levels of tumour necrosis factor-alpha (TNF-α). neopterin and interferon-alpha (IFN-α) were determined by immunoradiometric assays in 60 HIV-1⁺and 20 HIV-1⁻ subjects from Ethiopia. Swedish samples were used as reference material. The Ethiopian HIV-1⁺ subjects were found to have significantly increased TNF-α and neopterin, but not IFN-α levels. Increased levels of TNF-α and neopterin were frequently found in Ethiopian asymptomatic subjects (37% and 41%). and the concentration increased in patients with AIDS (83% and 90% respectively). The levels of the two substances and the proportion of patients with higher TNF-α values were lower in the corresponding Swedish subjects. The proportion of sera with raised levels of I FN-α was very low (asymptomatic 4%, and AIDS 7%) in Ethiopian subjects. These results suggest a very early increase in the TNF-α production and activation of the cellular immune response, and a low level of IFN-α synthesis in the natural course of HIV infection in Ethiopia. The aberrations may contribute to a rapid progress of immunodeficiency and cachexia often seen in Ethiopian patients.