The degree of oxygenation of a tumor is a major determinant of the effectiveness of radiotherapy. From animal experiments, it is known that hypoxia is common in tumors, that there can be marked heterogeneity in cellular oxygenation within a given tumor, and that the hypoxic fraction is influenced by tumor size and site. The three methods used in obtaining such information are discussed. They are not applicable to tumors in man, but other kinds of evidence suggest qualitatively that the patterns of oxygenation in human tumors are not dissimilar to those in animals. Reoxygenation of animal tumors appears to proceed rapidly after single conditioning radiation doses, but its rate and extent depend upon the size and scheduling of the conditioning dose(s). The importance of reoxygenation in determining the outcome of fractionated radiotherapy may be inferred from the results of recent tumor growth delay experiments wherein we have found that reoxygenation in the RIF-1 sarcoma is nearly complete by 24 hr. after the completion of 5 daily 5 Gy fractional doses.