Variations of the hypoxic fraction (HF) after single dose (13 Gy or 4 Gy) and during fractionated (5 fractions of 4 Gy, 1 or 2 fractions per day) radiation therapy were studied in SCC VII tumors implanted subcutaneously in the hind legs of C3H/He/Jms mice using the paired survival curve method. Whole-body irradiation was delivered to tumor-bearing mice without anesthesia or physical restraint, because both are known to increase the HF artificially. The HF decreased after a single 13 Gy dose in a biphasic fashion: extremely rapidly within 1 hr and comparatively slowly during the following 12-72 hr. On the other hand, nearly no fall of HF was observed in 24 hr following a single 4 Gy dose. Also, reoxygenation was found to occur more rapidly in the interfraction period as the number of fractions of 4 Gy increased irrespective of differences of interfraction time. However, the HF just before each radiation fraction was significantly higher than the pretreatment level for both fractionated regimens. Thus, the reoxygenation patterns observed after single low and high doses of irradiation were different from each other, and reoxygenation in each interfraction period did not always proceed in a similar manner to that after single low dose irradiation. Reoxygenation was facilitated as fractionated radiation therapy proceeded, but it was not sufficient for the HF to remain at a level comparable to that before irradiation.