The effect of cystone, a polyherbal ayurvedic preparation, on the nephrotoxicity and antitumor activity of cisplatin is studied in C57BL/6J mice bearing B16F1 melanoma. Intraperitoneal administration of cisplatin 6 mg/kg, resulted in significant reduction of body weight, elevation of blood urea nitrogen (BUN) and serum creatinine levels on day 5. Cystone was found to protect tumor-bearing mice from cisplatin-induced nephrotoxicity, when given i.p. 1 h before cisplatin. At 1000 mg/kg, it showed 46, 57 and 66% protection on body weight, BUN and serum creatinine levels, respectively. Treatment of cisplatin alone to tumor bearing mice resulted in significant antitumor activity as measured by tumor appearance, tumor volume and tumor weight. Pre-treatment with cystone (1000 mg/kg) did not reduce the antitumor activity of cisplatin. These results suggested that cystone protects against cisplatin-induced nephrotoxicity without interfering with its antitumor activity. The present study has many clinical implications in cisplatin chemotherapy.