We studied the effects of head-down tilt bedrest (HDT) on body weight, fluid and sodium homeostasis. A fluid load session with rapid intravenous infusion of 22 ml/kg body weight (BW) isotonic saline was performed before, during and after HDT. During the pre- and post HDT periods the test subjects were given a diet containing 2600 kcal/day. The energy intake was reduced to 2000 kcal/day during HDT. Water intake was kept constant at 40 ml/kg BW, sodium intake was 2.2 mmol/kg BW and protein intake was 1.4 g/kg BW, while the daily fat and carbohydrate intake was reduced during the HDT period. As expected plasma volume and BW changed rapidly in the beginning of HDT and during early recovery. A total body water loss of 0.6 l was observed within the second day after tilting. Plasma volume was reduced by 16% during HDT-bedrest. The time course of the body fluid loss paralleled a decrease in body sodium that then remained fairly constant during the HDT-bedrest period (except for the interference caused by the fluid loading on day S06). A restoration of body fluid and body sodium content occurred early in the recovery period. Fluid loading caused a negative fluid balance of 0.6-0.9 l over a 48 hr period following infusion regardless of the phase of the HDT study. These results demonstrate that under our strictly controlled conditions 1) HDT alters body fluid and sodium balances, 2) a standard fluid loading causes a net negative 3-day fluid balance during all phases of the study.