The ratio of reabsorption of osmotically free water to osmolal clearance in individual urine voids was about the same before and after short-term spaceflights (the points fall on the same regression line). This ratio was reduced after long-term flights, so that the regression lines for pre- and postflight values have different slopes. This change in the function relating the two factors was accompanied by increased vasopressin in blood plasma and probably was caused by altered cellular reaction to vasopressin. The decrease in the effect of vasopressin may have been caused by development of hypokalemia and hypercalcemia in the cosmonauts, and decrease in cellular potassium in the outer renal medulla (this effect was observed in experiments on rats after flights on biosatellites). We established that, in addition to cAMP, cGMP and inositol trisphosphate participate in cellular reactions to vasopressin. Increases in the concentration of cGMP and decrease in the formation of inositol trisphosphate in the presence of neomycin increase the hydro-osmotic effect of vasopressin. We hypothesize that modulation of the effect of vasopressin in cosmonauts is due to change in the functional state of their kidneys.