Alteration of the blood-brain barrier (BBB) by dysbaric exposure may have relevance in several areas of hyperbaric medicine. Drugs administered to persons exposed to dysbaric conditions, e.g., divers, compressed air workers, may penetrate the brain in amounts that could produce toxic or undesirable effects. Modification of the BBB may also have pathogenetic implications in decompression sickness. Furthermore, increased BBB permeability to certain potentially useful antitumor agents, antibiotics, and other compounds under dysbaric conditions may provide the basis for a new therapeutic approach. This report concerns the influence of dysbaric exposure on BBB permeability to an antibiotic. Tetracycline (5-40 mg/kg) was intravenously injected in 22 experimental rabbits (subjected to air compression-decompression) and 17 controls (kept at ambient pressure). Fluorescence microscopy and spectrometry revealed significantly greater tetracycline concentrations in 72.7% of the experimental brains. With the 5 mg/kg dose, the mean tetracycline concentrations was 0.17 micrograms/g in control brains and 0.33 micrograms/g in experimentals. These results indicate that dysbaric exposure increases BBB permeability to tetracycline. It appears that BBB alteration is related to intravascular gas bubbles but is independent of the development of decompression sickness. The conclusions of this investigation are pertinent to brain pharmacotherapy and may provide some new insight into the mechanism of decompression sickness. They also point to potential risks connected with drug administration under dysbaric conditions that can alter BBB permeability.