The present study was designed to potentiate the antineoplastic effects of cisplatin by combination with calmodulin antagonists [N-(6-amino-hexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5)] in nude mice bearing human ovarian carcinoma. Tumor growth of nude mice treated with W-7 or W-5 combined with cisplatin was significantly inhibited, compared to that of nude mice treated with W-7 alone, W-5 alone, or cisplatin alone. Although treatment with cisplatin alone markedly inhibited lytic activity of spleen cells from tumor-bearing nude mice against the tumor cells, the inhibitory effect was eliminated by combination with W-7 or W-5. There was no significant difference in survival time among untreated, cisplatin-treated, W-7-treated, and W-5-treated groups. Only when cisplatin was followed by W-7 or W-5 was a significant enhancement by W-7 or W-5 of the antitumor effect of cisplatin observed with respect to inhibition of tumor growth as well as prolongation of survival time.