The hypothesis that ECT produces selective effects on hypothalamic-pituitary activity was investigated by determining the effect of ECT on pituitary hormone release in nine depressed patients. After ECT there were massive and rapid increases in the plasma concentrations of nicotine- and oestrogen-stimulated neurophysin (NSN and ESN), prolactin (PRL) and adrenocorticotropin (ACTH), smaller increases in plasma luteinizing hormone (LH) and cortisol, a significant decrease in plasma growth hormone (GH) concentration but no change in plasma thyrotropin (TSH). There was significant attenuation of PRL responses with repeated ECT. The hormonal responses to ECT cannot simply be attributed to stress, since a similar pattern of increases in plasma hormone concentrations did not occur in psychologically normal patients in whom plasma hormone concentrations were measured during induction of anaesthesia and abdominal incision for cholecystectomy. Analysis of these hormonal responses in terms of the knowledge available on the neurotransmitter control of pituitary hormone release suggests that some of these hormonal responses to ECT may be mediated by the activation of serotonergic neurones, while others are probably due to direct stimulation of the neuroendocrine neurones themselves.