We present four head and neck cancer patients who apparently had rapid progression of clinically occult disease during or soon after undergoing hyperbaric oxygenation. This led us to review existing knowledge about the interaction of HBO with tumors. The literature can be summarized as follows: 1. HBO is a useful tool in several situations commonly encountered by head and neck surgeons-infections, radionecrosis, and wound-healing problems. 2. The use of HBO as a hypoxic cell sensitizer during radiation therapy has been extensively studied, with evidence supporting only marginal advantage to this logistically difficult undertaking. 3. Most reports regarding the interaction of HBO with transplanted tumor cells suggest no effect on tumor growth or metastases. 4. Studies of chemically induced carcinogenesis are less conclusive. Some evidence supports a role for HBO in enhancing growth of preexisting tumors. Better understanding of the interaction of HBO with existing tumors is required to ensure that informed choices-weighing potential risks and benefits of HBO treatment--may be made by head and neck surgeons and their patients. Further research into the interaction between HBO and tumor cells is warranted.