Effects of 5 weeks of horizontal bedrest on cardiovascular, musculoskeletal and thermoregulatory functions were studied in 10 healthy subjects. Bedrest decreased cross-sectional area and strength in the extensor muscles of the legs. The strength reduction, but not the atrophy, was as prominent in the hip- as in the knee-extensor muscles, suggesting that comprehensive quantitative studies on locomotor function after inactivity should include all joints of the lower extremities. Bedrest potentiated heat loss (increased sweating rate and decreased cold-induced vasoconstriction) and attenuated heat production (shivering), during immersion in 28°C water, suggesting that prolonged bedrest, and perhaps prolonged sojourns in space, may impair maintenance of normothermia in high heat-loss conditions. Bedrest increased the pain induced by markedly elevated local intravascular pressures in the arms and legs, which confirms the notion that G-induced arm pain may be aggravated in pilots returning to flying duty after being bedridden for a prolonged period. Bedrest potentiated pressure-induced increments in the diameters of arteries, arterioles and veins of the legs and, to a lesser extent, in the arteries and veins of the arms. Presumably, such marked increments in the pressure distension of the vessels in the lower limbs constitutes a salient mechanism underlying the reductions in orthostatic- and +Gz-tolerances following prolonged bedrest or space missions.