OBJECTIVES To test the hypothesis that hyperbaric oxygen (HBO) has no effect on tumor growth in a murine model of indolent in vivo prostate cancer. HBO means breathing pure (100%) oxygen under increased atmospheric pressure. METHODS Human prostate PC-3 cells were injected into 40 severe combined-immunodeficient mice. They were randomized to undergo 20 sessions of either HBO or normobaric air in standardized conditions and observed for 4 weeks before histologic assessment of any palpable tumors that had developed. The analysis of the developed PC-3 tumors included tumor volume, microvessel density, apoptosis-associated markers (ie, p53, p27), and the proliferative index (Ki-67). RESULTS The exposure to HBO at 2 arm for 20 treatment sessions, which comprised a daily 90-minute session, 5 d/wk, had no effect on the prostate cancer volume (P > .05). No differences were observed in tumor microvessel density, proliferative index, or apoptosis markets compared with the non-HBO group (P > .05). CONCLUSIONS HBO did not have a tumor stimulatory effect on prostate cancer and could potentially be used safely in conjunction with other therapeutic modalities. UROLOGY 73: 205-208, 2009. (C) 2009 Elsevier Inc.