Human melanoma cells have been used to evaluate whether stepdown heating (SDH) could increase the effectiveness of long-duration mild hyperthermia (LDMH). The effects of these treatments were also evaluated on cell survival and DNA polymerase inactivation. Short treatments (30 min) at 43 degrees C did not result in much SDH effect for subsequent protracted heating at 40 degrees C. The effect on DNA polymerases was also very small. However, heating at 44 degrees C for 30 min had a large SDH heating effect on subsequent heating at 40 degrees C and 41 degrees C. The SDH effect occurred mainly in the first 5-10 h of subsequent LDMH and, at longer heating times, the rate of cell killing was reduced. The 44 degrees C SDH effect was also observed on DNA polymerase inactivation. Comparing the degree of cell killing and polymerase inactivation showed a good correlation for the various SDH protocols.