The sensitivity of normal stroma to heat, irradiation and heat combined with irradiation has been studied using the tumour bed effect (TBE) assay. Irradiation before implantation led to a TBE. This TBE was dose dependent below 15 Gy, the TBE remaining relatively constant above 15 Gy. The interval (0-90 days) between irradiation and tumour implantation did not influence the magnitude of the TBE. Hyperthermia with large heat doses (45-60 min at 44 degrees C) before implantation may lead to a TBE. The interval between hyperthermia and tumour implantation proved to be very important. Our results show that the recovery from heat-induced stromal damage is very rapid. When the interval between hyperthermia and tumour implantation is 10 days or longer, no TBE could be observed. Irradiation combined with large heat doses (30-60 min at 44 degrees C) decreased the radiation-induced TBE. However, the combination of irradiation with mild heat treatments (15 min at 44 degrees C) could lead to a larger TBE than after irradiation alone. When hyperthermia was given prior to irradiation, the interval between heat and irradiation proved to be very important. With large intervals (21 days or longer) the TBE values were about the same as with irradiation alone. When heat was given after irradiation it always reduced the irradiation-induced TBE.