Previous research suggests synergism between RF radiation exposure and 2ME administration in pregnant rats (Nelson et al. Teratology 43: 621- 634, 1991). Concurrent administration of RF radiation, sufficient to maintain rectal temperatures at 42 degrees C for 30 minutes, and 150 mg/kg 2ME on gestation day 13 was found to increase significantly the incidence and severity of external malformations in rat offspring. The present study is designed to replicate and extend those observations by investigating the dose-effect relationships. Five durations of RF exposure (sham, 0, 10, 20 and 30 min) at 42 degrees C and five levels of 2ME (0, 75, 100, 125, and 150 mg/kg, p.o.) were administered to groups of six Sprague-Dawley rats on gestation day 9 or 13. Dams were sacrificed on day 20, and fetuses were removed serially, blotted dry, weighed, and examined for external malformations. Approximately one half of the fetuses were preserved in ethanol and the other half in Bouin's solution for later examination for skeletal or visceral malformations. Consistent with our previous observations, an enhancement of the incidence and severity of external malformations was dependent on the duration of RF radiation and dose of 2ME.