Functional properties of natural killer cells were analyzed in a 51chromium-release assay by modulating their activity with human beta-interferon using 1) peripheral mononuclear cells of 16 patients with carcinoma of the prostate and 7 healthy male donors, and 2) mononuclear cells from the periprostatic lymph nodes of 6 patients with stage pT2N0M0 prostatic cancer and 5 without malignancy. Cell lines EB 33, PC 3, DU 145 and CaKi 1 were used as target cells. Spontaneous cell-mediated cytotoxicity of peripheral mononuclear cells was depressed in patients with advanced prostatic cancer; however, the natural killer cells responded as those of the healthy controls to beta-interferon. The beta-interferon effect was time and dose dependent. In mononuclear periprostatic lymph node cells virtually no spontaneous cell-mediated cytotoxicity was detected. The reactivity of mononuclear periprostatic lymph node cells from patients with prostatic cancer was significantly less improved by beta-interferon stimulation than the mononuclear periprostatic lymph node cells of healthy subjects. The stimulation of mononuclear periprostatic lymph node cells by beta-interferon was reduced significantly compared to simultaneously tested autologous peripheral mononuclear cells.