To test the hypothesis that progesterone is involved in the regulation of dopamine release into hypophysial portal blood, female rats were adrenalectomized and ovariectomized at 1200 h on the day of proestrus and, immediately after the operation, injected sc with sesame oil or progesterone. Approximately 24 h later, hypophysial portal blood was collected and the plasma from this blood was analyzed for dopamine. The concentration of dopamine in portal plasma from rats given sesame oil or progesterone (50 mg) was 1.8 +/- 0.24 or 6.0 +/- 1.2 ng/ml (mean +/- SE), respectively. At the time of collection of portal blood, the progesterone concentration in arterial plasma was less than 0.8 ng/ml in rats given sesame oil and was 93 +/- 11 ng/ml in animals given progesterone. Conversely, the circulating concentrations of PRL was less (25 +/- 3 ng/ml) in animals given progesterone and higher (42 +/- 5 ng/ml) in animals given sesame oil. Twenty-four hours after the injection of progesterone (50 mg) into intact proestrous rats, the dopamine concentration in portal plasma was 5.8 +4- 1.29 ng/ml, a concentration which was significantly (P less thann 0.01) higher than that in untreated proestrous rats (1.1 +/- 0.24 ng/ml) but only slightly higher than that in untreated estrous rats (3.7 +/- 1.0 ng/ml). It is proposed 1) that progesterone administered sc can lead to an increased secretion of dopamine into hypophysial portal blood and 2) that the increased concentration of dopamine in portal plasma of intact pregnant rats relative to that of proestrous rats is, in part, a consequence of augmented progesterone secretion.