It has previously been shown that administration of basic fibroblast growth factor (FGF-2) to mice bearing xenografted human DLD-2 carcinomas produces significant increases in tumor growth rates and decreased intratumor hypoxia, effects which appear to be secondary to changes in the vasculature. In this study, we treated DLD-2 tumors with FGF-2 (ip, 0.25 mg/kg, q.i.d. x 7) beginning on day 15 after implantation, when average tumor volumes were 238 mm3. One day after cessation of administration of FGF-2 (day 22 after implantation, average tumor volume 1748.1 mm3), clamped tumors were given hyperthermia (42.5 degrees C, 60 min) by water bath heating. The slower-growing tumors in the control mice (sham-injected with Hanks' basic salt solution) were clamped and subjected to hyperthermia treatment at equivalent average tumor volumes (1882.7 mm3), which occurred on day 26 after implantation. Tumors in control groups were clamped but not heated. The time needed for neoplasms to grow to twice their volumes at the time of hyperthermia treatment was 68 days for the FGF-2-treated neoplasms and 47 days for the controls, while 26 and 31 days were needed for the control groups which were not treated with heat. The relative growth delay induced by hyperthermia is therefore 16 (47-31) days for control neoplasms and 42 (68-26) days for FGF-2-treated tumors. Therefore, tumors in the mice injected with FGF-2 were significantly more sensitive to the hyperthermia than controls, by a factor of about 2.6 (42/16). This result indicates that administration of growth factors such as FGF-2 to mice bearing tumors may produce an increased sensitivity of the tumors to hyperthermia.