Hyperbaric oxygen (HBO2) is used as adjunctive therapy for chronic osteomyelitis, yet its efficacy remains controversial. A recently developed rat model for osteomyelitis due to Staphylococcus aureus was used to compare the results of treatment with HBO2, cefazolin, a combination of both, or no treatment. For the induction of tibial osteomyelitis, S. aureus was inoculated into the medullary cavity. Arachidonic acid was used as the sclerosing agent. With that procedure, an infection rate of 96% was attained. For long-term antibiotic treatment, a port system was developed and implanted. Hyperbaric treatment alone reduced the colony-forming units (CFU) from 2.9 x 10(6) to 6.2 x 10(5) x g(-1) of tibial bone. The effect on the infection was more pronounced with antibiotic therapy alone, 10.5 x 10(4) CFU per g of tibial bone were measured. However, changes were most marked using a 4-wk combination therapy consisting of HBO2 and an antibiotic agent. The colony count was 2.7 x 10(3) CFU. Each of the treatment modalities resulted in a significant therapeutic effect. The results not only demonstrated the effectiveness of HBO2 in the treatment of osteomyelitis, but revealed a potential additive effect with the combination of HBO2 and an antibiotic.