Twenty-six people with symptomatic HIV-1 infection were screened for the presence of interferon (IFN)α and IFNα antibodies in their sera and the presence of the IFN-induced intracellular Mx-homologous protein in their peripheral blood leukocytes. Eleven people had measurable IFNα levels ranging from 1 to 40IU/ml. None of the sera tested was positive for IFNα binding or IFNα neutralizing antibodies in the assays employed. Twenty-five of the 26 people had significant levels of the Mx-homologous protein in their peripheral mononuclear cells. The Mx concentrations varied from 0.3 to 6U/ml in the people studied. IFNα-positive people had significantly higher levels of the Mx homolog than IFNα-negative people (P < 0.03). Furthermore, the Mx homolog content in Walter-Reed class 2 people was significantly lower than in Walter-Reed class 5/6 people (P < 0.01). Our results suggest that the IFN system is activated in more than 90% of the people with lymphadenopathy-associated syndrome, AIDS-related complex and AIDS. Since acid-labile IFNα can induce the Mx homolog in vitro endogenously produced IFNα seems likely to be responsible for the high Mx homolog levels detected.