The heat-induced interdependent changes of tumor blood flow, pO2, and pH decisively influence the therapeutic effect of hyperthermia (HT). This fact has induced us to determine simultaneously the frequency distribution of local pO2 values and the intratumoral pH in a xenotransplanted human sarcoma cell line at a normal blood glucose level and under hyperglycemic conditions before, during, and after HT. Two groups, one of 10 and one of 9 congenitally athymic nude rats with a subcutaneously implanted S117 human sarcoma into the right hind paw (mean tumor volume 5.3 cm3) were treated with local waterbath HT (tumor temperature 43 degrees C, 1 hr) alone or in combination with i.p. glucose injections (6 g/kg, 2 hr before the onset of HT). Tumor oxygenation remained improved throughout HT. Tumor pH did not decrease during HT. Hyperglycemia alone elicited a decrease of intratumoral pH and pO2, probably mainly due to hemoconcentration. The additional warming of the tumors (43 degrees C) during hyperglycaemia did not further decrease pO2 and pH. Silver stained sections of the tumors showed only a few very small necrotic areas, even in tumors of volumes up to 8 cm3. Our results indicate a well oxygenated tumor. In contrast to most tumors studied so far, hyperthermia in this tumor induces not only an initial increase of oxygenation but a lasting elevation of mean tumor pO2 for the duration of HT (up to 60 min).