Serum obtained from 57 healthy individuals and patients admitted to the hospital owing to diverse pathological causes, as well as serum from seven patients with AIDS and disseminated Mycobacterium avium complex (MAC) infection, were studied to determine the prevalence of IgG and IgM antibodies against surface proteins of M. avium complex. Immunodot assay to detect serum positivity against MAC and Western Blot technique in order to determine the MAC antigens eliciting antibody production were performed. Sera from 89 percent and 81 percent of the non-AIDS population had IgG and IgM antibodies against MAC antigens, respectively. In contrast, 43 percent and 71 percent of the AIDS population had IgG and IgM antibodies against MAC antigens, respectively, in the serum. To define further the antigens recognized by these naturally occurring antibodies, the serum of 14 non-AIDS and four acquired immunodeficiency syndrome (AIDS) patients were studied. Multiple antigens of MAC, with molecular weight ranging from 10 to 95 kilodaltons were recognized by IgG and IgM antibodies present in the sera. The IgM type antibodies were shown to react mainly against 10 kilodalton and 31 kilodalton antigenic protein, while the IgG type antibodies were produced mainly against the 10, 31, and 65 kilodalton proteins. Although the pattern of reaction was consistent between non-AIDS and AIDS populations, IgM antibodies were not detected against the 10 kilodalton protein nor were IgG antibodies detected against the 31 kilodalton protein in the AIDS population.