The non-uniform effects of hyperthermia observed in mouse intestine when heating is achieved by immersion of an exteriorized loop of jejunum in a hot bath were quantified. Intestinal damage was assayed by crypt destruction and correlated with local temperature and distance from major mesenteric blood vessels. The rate of rise of temperature during heating was much greater in regions far from blood vessels than in those close to vessels. Equilibrium temperatures in regions close to vessels were as much as 2 degrees C below liquid bath temperature. Such temperature differentials agreed well with those predicted from the heterogeneity observed in crypt destruction. Both histological and thermometric data suggest that major blood vessels may influence tissue temperature over a distance of approximately 2 mm and, within this region, temperature gradients of 1 degree C per mm may exist. These findings raise questions concerning the interpretation of previously reported data from water-bath heating of both tumours and normal tissues. They also emphasize the need for consideration of the influence of blood flow on heating patterns during hyperthermal treatment of patients.