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The effect of aging on vasopressin (VP) clearance was studied in male Fischer 344 rats 2 (young), 12 (adult) and 30 (old) months of age using in situ liver perfusion technique. The liver was perfused with Krebs-Henseleit bicarbonate buffer containing 1% bovine serum albumin and VP (2 ng/ml), at a constant temperature of 37 +/- 0.5 degrees C and a flow rate of 150 ml/h for 120 min. Expressed per whole liver and per gram tissue, VP declined exponentially over the studied period fitting well to the curve y = bekx (p = 0.0001) in all three groups. The analysis of covariance revealed the slope of the VP decay curve to be steepest in old rats, significantly different from that of young (p = 0.0001 expressed per whole liver or per gram tissue) and adult (p = 0.0001 and p = 0.001, expressed per whole liver and per gram tissue, respectively) rats. This suggests that, at least in male Fischer 344 rats, the hepatic clearance of VP was fastest in old rats.