Possible effects of GRF on somatostatin neurons and of somatostatin on GRF neurons were examined by measuring the effects of localised intracerebral injections of these peptides on growth hormone (GH) secretion. Serial GH concentrations were measured in plasma in unanaesthetized male rats chronically prepared with venous and intracerebral cannulae, before and after treatment with bilateral intracerebral injections of somatostatin or GRF in the preoptic anterior hypothalamic area (PO/AHA) and medial basal hypothalamus. Injections of 0.1 and 1 nmol of GRF in medial basal hypothalamus or 10 nmol somatostatin in the PO/AHA, respectively, had stimulatory or inhibitory effects on GH, which were assumed to be due to diffusion of the peptide from the injection site to the median eminence and pituitary gland. Injection of lower doses of somatostatin around GRF neurons in the medial basal hypothalamus were without significant effect on secretion of GH, but 0.1 nmol somatostatin in the PO/AHA resulted in an increase in GH concentrations from 128 +/- 61 to 524 +/- 103 ng/ml, p less than 0.02. Injections of GRF in lower doses amongst somatostatin neurons in the PO/AH or amongst GRF neurons in the medial basal hypothalamus were both without effect on GH secretion. We conclude that somatostatin may stimulate GH secretion by an effect on or close to somatostatin neurons in the PO/AHA. Somatostatin, though present in terminals on GRF neurons, is without effect at this site in our model. Furthermore, we have been unable to demonstrate any significant intrahypothalamic effect of GRF on GH regulation.