Plasma corticosterone clearance in anaesthetized rats was measured from the disappearance of radioactivity after a bolus injection of [3H]corticosterone. Mean fractional clearance rates were significantly (P less than 0.05) reduced after a 48 h fast, by 32 and 22% for males and females respectively. Plasma corticosterone concentrations were increased by fasting in both sexes. Corticosterone secretion rates, calculated as the product of fractional clearance and plasma corticosterone concentration, did not differ between fed and fasted groups in either sex. The mean activity (U/liver) of the rate-limiting enzyme for corticosterone degradation, hepatic 4,5-dihydrocorticosterone:NADP+ delta 4-oxidoreductase, was significantly reduced by 51 and 78% after fasting in males and females respectively. This was due to changes in both the soluble and microsomal forms of the enzyme. The binding capacity of corticosterone-binding globulin in plasma was significantly reduced by fasting in females (P less than 0.001), but was not altered in males. The results suggest that reduced hormone clearance is the dominant cause of fasting hypercorticosteronaemia in the rat.