The sensitivity of two human pancreatic adenocarcinomas (Capan-1 and Capan-2) to heat and heat combined with chemotherapy was studied using xenografts of the tumors in the foot of athymic nude mice. Heat was applied by immersion of the tumor in a water bath at 43.5 degrees for 1 hr. A single i.p. dose of mitomycin C, cisplatin, 5-fluorouracil, or 0.9% NaCl solution was given at 1 hr prior to treatment. Heat treatment alone significantly suppressed tumor growth (p less than 0.001), with 35% of the tumors showing complete regression. Combined treatment using heat plus chemotherapy yielded significantly greater suppression of tumor growth (p less than 0.05) with mitomycin for both tumors and with cisplatin or 5-fluorouracil for Capan-1. Combined treatment also gave higher rates of complete tumor regression: 55 and 64%, respectively, for Capan-1 and Capan-2 as compared with 18 and 47% for the respective tumors treated by heat alone. These observations suggest that human pancreatic carcinomas are sufficiently sensitive to heat combined with chemotherapeutic treatment to warrant a clinical trial of these modalities.