Twenty horses with 30 lesions were studied to evaluate the effects of intratumoral chemotherapy with cisplatin in sesame oil on equine sarcoids (n = 19), squamous cell carcinomas (n = 7), and squamous cell papillomas (n = 4). Treatment consisted of 4 sessions of intratumoral cisplatin chemotherapy at 2-week intervals. A controlled-release formulation of cisplatin in sesame oil was used to limit drug egress from the injection site. Mean dosage per session was 0.97 (+/- 0.17, SEM) mg of cisplatin/cm3 of tumor tissue treated for tumor volumes ranging from 10 to 20 cm3. Dosage tended to be slightly higher for smaller tumors and slightly lower for larger tumors. Tumor regression was observed in all horses. Complete response was observed in 18 of the sarcoids, 5 of the squamous cell carcinomas, and 4 of the squamous cell papillomas. The mean relapse-free interval was 21.6 and 14 months in horses with sarcoid and carcinoma/papilloma, respectively. The 1-year relapse-free rates were 87 and 65% for equine sarcoid and carcinoma/papilloma, respectively. In horses with relapse, 70% had tumor recurrence outside the treated field. Cisplatin-related local toxicosis was minimal. Intratumoral cisplatin chemotherapy was found to be a practical and effective treatment of sarcoid and squamous cell carcinoma/papilloma in horses.