Following our pilot study, we measured gonadotropin release in response to naloxone challenge in 17 female and 19 male neuroleptic-free, physically well, psychotic patients and compared them with age, sex and menstrual cycle phase matched controls. A total of six 10ml blood samples were taken at 20 min intervals via a peripheral intravenous cannula. Two baseline samples were followed by administration of 10 mg intravenous naloxone over 5 mins. Radioimmunoassays of Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), estrogen, progesterone and testosterone were performed.Baseline levels were compared using 2-sample independent t-tests and response curves using repeated measures ANOVA. Female luteal patients had higher baseline levels of FSH than controls while male patients showed higher baseline LH levels (p<0.05). Hormone response to naloxone challenge was significant for LH in males (p<0.0005) and females (p<0.005) and for FSH in females (p<0.005) but not males. No significant differences were found between patients and controls for testosterone and progesterone. The female patients had a lower mean baseline estrogen level compared with female controls (300 mmols/L cf 380 mmols/L). Overall psychotic females demonstrated some hypergonadotropinisim which may be expressed as hypoestrogenism. Low estrogen levels have been implicated in the onset or exacerbation of psychosis.