The immunosuppressive properties of the hormonal and/or secretory milieu or tumorelaborated factors (in the case of carcinoma) of the prostate have been hypothesized as contributory to the natural history of prostatic cancer. The effect of normal human seminal plasma (HuSPl) on immunity to tumor-associated antigens in patients with prostatic cancer has been evaluated by leukocyte adherence inhibition, a suggested in vitro correlate of cellular immunity. Significant (p < 0.01) suppression of immunity to malignant prostate ranging from 16 to 80% of the level of reactivity obtained with unincubated patients’ leukocytes was observed in 22 (88%) of 25 patients following preincubation of their leukocytes with HuSPl. Suppression of tumor-associated immunity by HuSPl provides further evidence to studies by others demonstrating SPI suppression of a range of immune responses in normal murine and human hosts. In addition to the possible biological implications of the immunosuppressive properties of SPI, e.g., as directed toward preservation of the species, whereby under normal conditions tolerance to spermatozoa in the male tract and in the female tract, following coitus, is maintained, it is hypothesized on the basis of collation of studies demonstrating experimental prostatic cancer from sensitization by spermatozoa and the relationship of prostatic cancer to repression of sexual activity, that SPI may play a significant role in the natural history of prostatic cancer.