Pulmonary and cardiovascular responses to simulated weightlessness, i. e. 6 degrees head-down tilt bedrest (HDT) were investigated in six healthy male volunteers (mean age 26 yrs). Pulmonary diffusing capacity, functional residual capacity, pulmonary capillary blood flow, and lung tissue volume were measured by inert gas rebreathing. Heart rate and mean arterial blood pressure were obtained from finger blood pressure readings using a plethysmographic technique (Finapres). The short-term (20 min) response to HDT consisted of a 22% increase in pulmonary blood flow, and 13% and 31% falls in blood pressure and heart rate relative to standing. Functional residual capacity fell by 33%, while lung tissue volume increased insignificantly. Subsequent measurements during 10 days of HDT and 5 days of recovery revealed no further changes in lung volume, lung tissue volume, or blood pressure. However, diffusing capacity fell gradually and remained 4%-5% below baseline values after the 7th day of bedrest and during recovery (p less than 0.05). Pulmonary blood flow decreased by 16% during head-down bedrest and recovered partially within the following 5 days (p less than 0.05). We conclude that during and after simulated weightlessness marked alterations in cardiovascular function and marginal affections of gas exchange can be demonstrated already at rest. They may be considered as contributing factors to orthostatic and exercise intolerance observed after space flight.