The effect of oral administration of sulpiride on PRL secretion and initiation of puerperal lactation was studied in 130 randomly selected primiparous nursing mothers. Sixty-six women were given 50 mg sulpiride orally twice a day during the first 7 days of the puerperium (sulpiride group). Sixty-four women were given a placebo in the same way (control group). The mean (+/-SE) total milk yield during the first 5 postpartum days in the sulpiride group (1211.7 +/- 65.0 ml) was significantly greater than that in the control group (916.0 +/- 66.0 ml). Every other day determinations of serum PRL levels revealed significantly higher concentrations in the sulpiride group than in the control group. A single oral dose of 50 mg sulpiride raised serum PRL levels for 12 h, with a peak level at 2 h after dosing in 7 women on the second postpartum day. These data suggest that sulpiride given orally promotes the initiation of lactation in puerperal women by stimulating PRL secretion.