Objective: To re-examine the controversial possibility that prolactin exerts renal effects, using recombinant mouse prolactin (rmP), in the presence and absence of circulating vasopressin. Design: In experiment 1, the renal effects of rmP were examined in anaesthetized Brattleboro rats with hereditary hypothalamic diabetes insipidus (BDI) lacking circulating vasopressin and normal animals of the parent Long Evans (LE) strain. In experiment 2, salt and water excretion were studied in fluidloaded normal Sprague±Dawley (SD) rats, some of which received rmP. Methods: In experiment 1, BDI and LE rats maintained in fluid balance were infused i.v. with each of three concentrations of rmP (10, 20 and 40 mg/ml per h) or maintained on 150 mmol/l NaCl vehicle (controls). In experiment 2, the SD rats were infused with 75 mmol/l NaCl in order to induce a state of diuresis comparable to that of BDI rats, some of them then receiving the rmP i.v. Results: A profound rmP-induced dose-dependent decrease in urine excretion P , 0X005 and a lesser decrease in sodium excretion in the BDI rats was in marked contrast with the small but significant increase in urine excretion in the LE rats compared with controls P , 0X025X The rmPinfused fluid-loaded SD rats also demonstrated a significant P , 0X05 dose-related antidiuresis compared with the control animals, in addition to a decrease in sodium excretion. Conclusions: These results show that prolactin has a profound antidiuretic effect in the absence of circulating vasopressin. In contrast, when vasopressin is present in the circulation rmP has a small, but opposite, diuretic effect. Thus the use of a recombinant prolactin has provided evidence for renal effects of this hormone which are modified in the presence of the circulating neurohypophysial hormone vasopressin.