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Changes in metabolic parameters of healthy subjects were studied during experimental 4-to 21-day courses of simulated diving in hyperbaric normoxic (oxygen-helium), hyperoxic (oxygen-nitrogen-helium), and argon-containing gas mixtures with different oxygen contents. The blood concentrations of primary substrates and activity of enzymes were measured spectrophotometrically. In most cases, the clinical and biochemical parameters of the blood remained within normal clinical ranges and exhibited significant individual variations. Long-term simulated deep dives (>200 m) resulted in changes in lipid metabolism expressed as an increase in the plasma concentrations of triglycerides, low-density lipoproteins, and polyunsaturated fatty acids. No significant changes were found during experimental 70-m dives performed according to recompression treatment table with the use of a hyperoxic helium-containing gas mixture. In contrast, long-term exposure to a normoxic argon-containing mixture at a pressure of 5 msw caused a significant increase in the blood contents of triglycerides, total cholesterol, and glucose, as well as a smaller increase in the activities of several tissue enzymes. At the same pressure, hypoxic oxygen-nitrogen-argon and oxygen-nitrogen mixtures did not affect the majority of clinical and biochemical parameters examined. However, in some subjects, they increased the atherogenicity index, concentrations of triglycerides, and activities of lactate dehydrogenase and alkaline phosphatase. The absence of any pathological changes in clinical and biochemical parameters of the blood indicates that both gas mixtures are safe and can be used in barochambers. Episodic changes in lipid metabolism and enzyme activities observed in healthy subjects exposed to helium-and argon-containing gas mixtures can be interpreted as a reversible hepatic dysfunction due to the high pressure. The extent of the changes in the parameters of lipid metabolism in the blood is determined by the magnitude of the overpressure and the duration of the exposure.