The effects of indomethacin, an inhibitor of prostaglandin synthesis, were studied on the sodium and fluid balance of rats kept on a normal diet and physiologic saline for two weeks. Under the effect of indomethacin the inulin compartment (extracellular space) and Na(24)-compartment expanded from 20.5 plus or minus 4.1 to 25.2 plus or minus 5.1 ml per 100 g, (p.less than 0.001); and from 31.9 plus or minus 2.8 to 37.0 plus or minus 5.6 ml per 100 g, (p less than 0.001), respectively, and the exchanged amount of Na+ increased from 4.33 plus or minus 0.5 to 5.01 plus or minus 1.03 mEq per 100 g, (p less than 0.02). On the other hand, fluid and Na+ uptake and excretion were unaffected. Haematocrit and plasma protein levels decreased (from 42.5 plus or minus 2.98 to 38.6 plus or minus 5.2%, p less than 0.01; and from 5.41 plus or minus 0.67 to 5.01 plus or minus 0.47 g/dl; p less than 0.05, respectively). The experimental findings supported the assumption that (a) under conditions of saline loading the prostaglandins might play a role in the mechanism of natriuresis and their absence might lead to sodium and water retention. (b) The indomethacin induced transient reduction in salt and water excretion could be restored by the combined effect of volume regulating reflex mechanism and physicochemical factors (haemodilution).