The effect of exposure of organisms to systemic hyperthermia on induction of tolerance to the lethal effect of subsequently assigned systemic hyperthermia was studied in mice. The length of time of the pretreatment at 42.0 +/- 0.2 degrees C (core body temperature) was 5, 10 or 15 mn. The temperature of the second systemic hyperthermia was 42.0 +/- 0.2 degrees C and 43.5 +/- 0.2 degrees C. In mice which had no experience of systemic hyperthermia, lethal dose required to kill 50% of animals at 42.0 degrees C and 43.5 degrees C, namely LD50, 42 degrees and LD50, 43 degrees 5 was 43 and 8.5 mn, respectively. While, in mice which had received the pretreatment at 42 degrees C for 10 mn, the LD50, 42 degrees was 97 mn one day after and 48 mn two days after the pretreatment. In mice which had received the pretreatment at 42 degrees C for 5, 10 or 15 mn, the LD50, 43 degrees 5 was 17, 20 and 19 mn one day after the pretreatment, and 10, 10 and 6 mn two days after the pretreatment, respectively. With the data obtained, thermotolerance ratio (TTR) was calculated. The maximum TTR of 2.35 was obtained in mice examined one day after the pretreatment at 42.0 degrees C for 10 mn.