A pathogenic retrovirus (HTLV-III) has recently been isolated in the seminal plasma (SP) of patients with AIDS. In order to test whether SP may influence non-specific immunity we compared the influence of SP on the phagocytic release of lysozyme, chemotaxis and chemiluminescence. SP inhibited the release of lysozyme from granulocytes in a log-linear fashion; incubation with undiluted SP resulted in about 50% inhibition. Chemotaxis of granulocytes remained stable under the influence of SP. Chemiluminescence of both granulocytes and monocytes was completely blocked by undiluted SP; 1000-fold dilutions still caused an inhibition of about 20%. The separation of SP by column chromatography yielded fractions with a molecular weight of 10(4) to 2 X 10(4), 10(5) to 4 X 10(5) and greater than 10(6) inhibiting chemiluminescence. A cell-free chemiluminescent system showed the reduction of chemiluminescence to be based to a large extent on quenching of the photons generated. Our results indicate that SP possesses potent properties that suppress non-specific immunity, possibly an important predisposing factor to AIDS.