Indomethacin and salicylates are considered to be specific inhibitors of prostaglandin (PG) synthesis. If their mechanism of actin is common then similar effects would be expected in organs capable of PG production. In the present investigation the effects on renal and intrarenal haemodynamics by indomethacin and Na-salicylate were studied and compared in anaesthetized (nembutal) dogs using SAPIRSTEIN's technique. Indomethacin (4 mg per kg) raised blood pressure while cardiac output remained unaffected. Sodium salicylate (200 mg per kg) also increased blood pressure, however, this was associated with increased cardiac output. Renal blood flow was depressed by indomethacin, whereas it was not influenced by Na-salicylate (RBFcontr. = 411 +/- 97; RBFindo. = 292 +/- 53, p less than 0.01; RBFNa-salic. = 468 +/- 110 ml per min per 100 g). Renal resistance was augmented after indomethacin and unaltered by Na-salicylate (Rcontr. = 1.96 +/- 0.43; Rindo. = 3.03 +/- 0.97, p less than 0.001; RNa-salic. = 1.91 +/- 0.49). Indomethacin provoked an intrarenal blood flow redistribution, while no such effect was seen by Na-salicylate. Salt and water excretion was markedly suppressed by indomethacin, whereas Na-salicylate exhibited diuretic and natriuretic actions. It is concluded that the two agents exert their actions on renal haemodynamics and salt and water excretion by different mechanisms. The differential responses might be accounted for by the finding that Na-salicylate fails to inhibit renal PG-production.