Bed rest studies which simulate weightlessness have demonstrated marked changes in the state of hydration of subjects as well as decrements in aerobic capacity. These two phenomena may be linked through increases in blood viscosity which is altered by a loss of free water and which, in turn, influences blood flow needed for aerobic muscular work. This study examines changes in the rheologic properties of blood which attend changes in plasma volume with bed rest in humans and correlates these changes with alterations in aerobic capacity. Eight healthy human subjects were studied on the 6th day of bed rest during two consecutive 10-d bed rest periods separated by a 14-d recovery interval designed to simulate the flight-layover schedule of shuttle astronauts. Plasma viscosity was measured with a Wells-Brookfield viscometer, plasma volume by dye dilution, and maximal aerobic capacity (VO2max) by recumbent cycle ergometry. Bed rest resulted in significant increases in hematocrit and in total plasma protein concentration and fibrinogen concentration, both of which contribute to an elevation in plasma viscosity. The greater than 20% increase in fibrinogen concentration was much greater than could be explained by hemoconcentration. VO2max decreased significantly in the first but not the second bed rest cycle. In many individuals, a decrease in plasma volume and aerobic capacity was coupled with elevated plasma viscosity and hematocrit; however, significant correlations between these variables were lacking. Although significant rheologic perturbations do occur with bed rest, in this study, blood viscosity elevation failed to directly correlate with the reduction in VO2max.(ABSTRACT TRUNCATED AT 250 WORDS)