The heat sensitivity of the murine jejunum from C3H/HeJ mice and its capacity to develop thermotolerance were measured. Exteriorized loops of murine jejunum were heated in water baths at temperatures of 43-46 degrees C for various times. Animal mortality was used to calculate the median lethal dose by day 7 (LD50/7) in minutes as a function of temperature. The LD50/7 value was independent of the length of the intestinal loop, the presence of serum in the heating medium, prior starvation of animals, and fluid replacement post heating. The time-temperature plot for the LD50/7 values had an exponential slope constant of -0.71 degrees C-1, similar to that for other normal tissues. A heat treatment of 5 minutes at 45 degrees C increased the LD50/7 (total time at 45 degrees C) from 5.9 minutes to 13.0 and 15.6 minutes for 1- and 3-day fractionation intervals, respectively. Death after intestinal heating was associated with septicemia and reached a peak on days 2 and 3 post hyperthermia. Gentamicin (0.1 mg/mouse/day) increased the LD50/7 at 45 degrees C from 5.9 to 9.6; however, septicemia was still noted in dying, gentamicin-treated mice. Additional antibiotics did not further increase the LD50/7. Heat fractionation with gentamicin increased the LD50/7 (total time at 45 degrees C) to 23.0 and 12.5 minutes at 45 degrees C for 1- and 3-day intervals, respectively. These data suggest that thermotolerance plays a significant role in the intestinal heat response, but that the heat damage to intestinal barriers against bacterial septicemia may be superimposed on the cellular damage to the crypt-villus system.