The skin of mouse feet was used to study the effects of hyperthermic treatment, either alone or combined with irradiation. The present experiments show that a priming heat treatment induces resistance both to a subsequent heat treatment and to a subsequent combined irradiation-heat treatment. The development of resistance to a combined irradiation-heat treatment after a priming heat treatment (30 min at 43 degrees C) was relatively slow (18-24 h) compared to development of resistance to a heat treatment without irradiation (6 h). Misonidazole, when administered prior to heat treatment only, did not influence the heat-induced skin reaction. However, when misonidazole was administered prior to combined irradiation-heat treatment, a slight but significant increase of the skin reaction was observed. Also, in combination with misonidazole resistance to combined treatment was observed by a priming heat treatment.