1. The effects of bed rest on the cardiovascular and muscular parameters which affect maximal O2 consumption (VO2,max) were studied. The fractional limitation of VO2,max imposed by these parameters after bed rest was analysed. 2. The VO2,max, by standard procedure, and the maximal cardiac output (Qmax), by the pulse contour method, were measured during graded cyclo-ergometric exercise on seven subjects before and after a 42-day head-down tilt bed rest. Blood haemoglobin concentration ([Hb]) and arterialized blood gas analysis were determined at the highest work load. 3. Muscle fibre types, oxidative enzyme activities, and capillary and mitochondrial densities were measured on biopsy samples from the vastus lateralis muscle before and at the end of bed rest. The measure of muscle cross-sectional area (CSA) by NMR imaging at the level of biopsy site allowed computation of muscle oxidative capacity and capillary length. 4. The VO2,max was reduced after bed rest (-16.6%). The concomitant decreases in Qmax (-30.8%), essentially due to a change in stroke volume, and in [Hb] led to a huge decrease in O2 delivery (-39.7%). 5. Fibre type distribution was unaffected by bed rest. The decrease in fibre area corresponded to the significant reduction in muscle CSA (-17%). The volume density of mitochondria was reduced after bed rest (-16.6%), as were the oxidative enzyme activities (-11%). The total mitochondrial volume was reduced by 28.5%. Capillary density was unchanged. Total capillary length was 22.2% lower after bed rest, due to muscle atrophy. 6. The interaction between these muscular and cardiovascular changes led to a smaller reduction in VO2,max than in cardiovascular O2 transport. Yet the latter appears to play the greatest role in limiting VO2,max after bed rest (> 70% of overall limitation), the remaining fraction being shared between peripheral O2 diffusion and utilization.