Gossypol, a polyphenolic compound known to interfere with spermatogenesis, was found to have differential cytotoxic effects on normal and malignant melanocytes in culture. Ultrastructurally it caused marked swelling and vacuolization of mitochondria; there was an almost complete loss of cristae but the outer mitochondrial membrane was retained. The cytotoxicity seemed to be selective for actively proliferating cells, regardless of normal or malignant origin. An endothelial cell line (RF/6A) derived from the choroid-retina of the eye of a rhesus fetus was extremely sensitive to its toxic effect. The mechanism of action is still unknown. The fact that mitochondria are predominantly damaged suggests that toxicity involves a perturbation of energy metabolism and the membrane transport system.