Suramin, an antiparasitic agent which has been shown to block the stimulatory effect of growth factors on certain cancers, is currently being evaluated in clinical trials and as an antineoplastic agent in patients with advanced prostate carcinoma. Preliminary studies suggested that suramin inhibits the growth in vitro of human prostate carcinoma. The present study was performed in order to evaluate the effect of suramin, recombinant human tumor necrosis factor (TNF), interferon gamma and the combination of suramin plus TNF or interferon gamma on proliferation of PC-3, a human, hormone unresponsive prostate carcinoma cell line. In medium containing 2% fetal calf serum (FCS) suramin, at doses of 10 microM, 30 microM and 100 microM (levels readily achievable in humans) inhibited proliferation of PC-3. TNF, at a concentration of 500 units/ml., induced an approximately 50% inhibition of growth of PC-3. The combination of suramin plus TNF induced a greater inhibition of growth than did either agent alone, even at the low dose of 10 microM suramin. Interferon gamma, 500 units/ml., inhibited PC-3 growth. However, the combination of interferon gamma plus suramin (30 microM) induced less inhibition of proliferation than did interferon gamma alone. These results may serve as a rationale for clinical trials employing the combination of TNF plus suramin in patients with advanced prostate carcinoma.