This study was undertaken to examine the effects of atrial natriuretic peptide (ANP), dopamine, and ouabain, which each are considered to be a kind of natriuretic factor, on aldosterone synthesis in vivo and in vitro. In the in vivo experiments, during infusion of one of the natriuretic factors, ANP (64 pmol X min-1 X kg-1), dopamine (20 nmol X min-1 X kg-1) or ouabain (684 II pmol x min-1 x kg-1), the stimulatory action of angiotensin (20 pmol X min-1 X kg-1) or adrenocorticotropin (ACTH, 7 pmol X min-1 X kg-1) on aldosterone synthesis was investigated in 36 anaesthetized (pentobarbital, 40 mg/kg, iv) female rabbits. In the basal condition, aldosterone synthesis was suppressed slightly by each of the natriuretic factors. The stimulatory actions of angiotensin II and ACTH on aldosterone synthesis were significantly attenuated by pre-treatment with ANP and dopamine. However, ouabain infusion did not induce any changes in the synthesis of aldosterone, 18-hydroxycorticosterone (18-OHB), and corticosterone (B) in either the basal or the stimulated conditions. For the in vitro experiments, rabbit adrenal glomerulosa cells (10(5) cells/tube) were used. The effects of ANP and dopamine on the aldosterone synthesis revealed results identical to those from the in vivo study. However, in contrast to the in vivo study, ouabain completely inhibited the synthesis of aldosterone, 18-OHB and B. The above results obtained in vivo and in vitro suggest that ANP inhibits corticosterone methyloxidase II activity and dopamine inhibits corticosterone methyloxidase I activity. However, from the present study we were unable to specify the action of ouabain on the synthesis of aldosterone and its related substances.