The effects of step-up (42 leads to 44 degrees C sequence) and step-down (44 leads to 42 degrees C sequence) heating were studied on the skin of C3H/He mouse feet. Skin damage in mouse feet exposed to 44 degrees C alone became proportionally more severe with increasing exposure time, while it was slight or not observed at 42 degrees C for up to 2 hr. Preheating to 42 degrees C for 60 or 120 min (step-up) had little effect on the damage from 30-60 min exposure at 44 degrees C, but increased the damage seen with 90 min at 44 degrees C. However, skin damage was markedly enhanced by exposure to step-down heating. On the other hand, thermal resistance was induced in the mouse skin by 44 degrees C fractionated treatments. The induced thermal resistance reached a maximum with a 1 day interval, and then disappeared after a 3 day interval. In another fractionation schedule of step-down heating, the enhanced skin damage which was observed when here was no interval, recovered rapidly and attained an additive response within a 1 day interval. No thermal resistance was observed.