OBJECTIVE--To test the hypothesis that affective psychosis after childbirth is associated with an altered sensitivity to dopaminergic stimulation. DESIGN--Prospective study of pregnant women at high risk of developing an affective psychosis after childbirth. Clinical assessments in pregnancy and after delivery were made by using a semistructured interview (schedule for affective disorders and schizophrenia) and psychiatric illnesses were categorised according to operational criteria (research diagnostic criteria). SETTING--Obstetric and psychiatric departments in and around Greater London. SUBJECTS--29 pregnant women with a history of bipolar or schizoaffective psychosis and 47 control pregnant women. Of these, 16 from each group participated in a growth hormone challenge test and the results for 15 women in each group were analysed. INTERVENTIONS--On the fourth day postpartum women participating in the hormone challenge test were given a subcutaneous injection of a small dose (0.005 mg/kg) of the dopamine agonist apomorphine. MAIN OUTCOME MEASURES--Growth hormone secretion in response to apomorphine as an index of the functional state of hypothalamic dopamine receptors. RESULTS--Eight of the 15 women at risk of psychosis subsequently had a recurrence of illness (five bipolar, one schizomanic, and two major depressive illnesses); these women had significantly greater growth hormone responses to apomorphine than the seven at risk women who remained well and the 15 controls, and there were no significant differences between groups in average baseline growth hormone concentrations. The mean (SD) concentrations for women with recurrence, women at risk who remained well, and control women respectively were: average baseline concentrations 1.06 (1.14), 1.44 (1.39), and 0.90 (1.34) mU/l; peak increase in concentrations 13.68 (12.95), 3.46 (4.68), and 3.40 (3.83) mU/l (between group difference p less than 0.05); average increase in concentrations 6.74 (7.01), 1.78 (3.39), and 1.40 (2.05) mU/l (p less than 0.05). CONCLUSIONS--The onset of affective psychosis after childbirth was associated with increased sensitivity of dopamine receptors in the hypothalamus and possibly elsewhere in the brain. Such changes may be triggered by the sharp fall in circulating oestrogen concentrations after delivery.