The immunosuppressive effects of human seminal plasma are mediated by several factors. The prostaglandins (PG) of the E series (PGE and 19-hydroxy PGE) predominate and raise intracellular cAMP in leukocytes. By this mechanism they suppress lymphocyte proliferation, natural killer (NK) cell activity and are likely to modify cytokine release from antigen presenting cells (APC). In this way, acquired and innate responses (including immune surveillance) in the reproductive tract will be curtailed, at least temporarily, after intercourse. Semen contains several inhibitors of complement and a unique reservoir of CD59, a major complement inhibitor, is found on the prostasomes which are sub-micron organelles with lipid membranes. The prostasomes also inhibit lymphocyte proliferation and the activity of phagocytic cells. Other suppressive agents are also present in semen and may exert specific effects, for example, transforming growth factor-β which may inhibit primed responses to antigen, and receptors for Fc fraction of γ-globulin which might bind inflammatory agents. A thesis is proposed that the balance between maximum chances of survival for spermatozoa and minimum chances for micro-organisms has been disturbed by an increased use of non-barrier contraception, an increase in population mobility and sexual contact and the arrival of new diseases such as AIDS. A further major concern is that following infection of cells of the cervix with virus, repeated exposure to human seminal plasma may accelerate the progression of disease.