Growth of Staphylococcus aureus ATCC 6538P was studied in stationary broth cultures (11 mm deep) exposed to hyperbaric oxygen (100% O(2) at 3 atm absolute). The minimal inhibitory concentration (MIC) of the following antibiotics was determined after exposure to high-pressure oxygen (HPO) for 3, 6, and 12 hr: penicillin, streptomycin, tetracycline, oxytetracycline, kanamycin, and cephalothin. Logarithmic growth during exposure to HPO was retarded 60%. Air at 3 atm absolute did not retard growth. The longer the exposure of tube dilution tests to HPO, the lower the MIC. Regardless of the antibiotic used, MIC values relative to 100% for unexposed controls were similar for given exposures, and averaged 73% after 3 hr of exposure to HPO, 53% after 6 hr, and 34% after 12 hr. Similar enhancement with HPO and an iodophor suggests occurrence of a general phenomenon with antibacterial agents. Although HPO alone is primarily bacteriostatic, combined therapy with antibiotics and HPO may be useful against bacterial infections because the therapeutic effectiveness of a maximal dosage of antibiotic could be increased.