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Atrial natriuretic factor (ANF) has been shown to increase circulating cortisol levels in cannulated, free-swimming seawater (SW)-adapted flounders. Increases were apparent within 30 min of i.v. injection of human ANF hANF; 10µg/kg bw) and the increase in plasma cortisol was maintained throughout the 5h experimental period. No such increase was observed in vehicle-injected controls. This apparent steroidogenic effect of ANF was supported by an ANF-induced increase in in-vitro secretion of cortisol by interrenal tissue from SW-adapted trout. By contrast hANF had no significant effect on tissue derived from freshwater adapted trout. An ANF-induced increase in plasma cortisol by a direct effect on interrenal steroidogenesis in SW teleosts would be an appropriate response for survival in hypertonic media.