In order to gain insight into mechanisms governing the development of tumor hypoxia, malignancies derived from spontaneously tumorigenic or ras-transformed cell lines were grown in nude mice. As a rule, tumors with ras oncogenes exhibited rapid growth rates and large areas with low pO2 readings even at small tumor sizes. The slow proliferation rate of a spontaneously tumorigenic cell line was consistent with more adequate tissue oxygen levels. In all lines, hypoxia was accentuated at larger tumor sizes. These results demonstrate that ras transformation can lead to accelerated proliferation rates and is then concomitant with the development of pronounced tumor hypoxia.