Saturation diving involves exposure to elevated partial pressure of oxygen (Po2) and high pressure. The present work demonstrated that hyperoxic exposure for up to 72 h had significant effects on human lung fibroblasts. Forty to sixty kPa Po2 had severe acute toxic effects, and 60 kPa O2 reduced plating efficiency approximately 96% and completely inhibited cell proliferation. Long-term toxic effects were observed as a persistent reduction of cell growth rate after 24 h exposure to 60 kPa O2 in helium, suggesting genetic effects or induction of cellular senescence. No effect of high pressure per se was observed in this respect. Cellular glutathione was increased up to a plateau 40-50% above control level after an initial decrease, which may indicate toxic effects during the GSH depletion period. The glutathione egress increased even more than the intracellular level after exposure to these conditions. The effects on glutathione were growth state specific with the highest response in exponentially growing cells. Slight protective effects of high pressure were noted in a cell growth assay, correlating with a reduced response on the glutathione level. The results support previous studies indicating that hyperoxia is the main contributor to the adverse effects of exposure to high Po2 and high pressure and point to the involvement of glutathione in the cellular detoxification of reactive oxygen species under these conditions.