The effects of human growth hormone-releasing factor (hGRF) and somatostatin on growth hormone (GH) and prolactin (PRL) secretion in perifusion of dispersed cells of human GH-secreting adenomas, obtained from seven acromegalic patients with hyperprolactinaemia, were examined. Six adenomas stained for both GH and PRL on immunohistochemical examination, and one contained only GH. GH release was consistently stimulated in a dose-dependent manner by hGRF (0.01, 0.1 and 1.0 nM) in all seven adenomas studied. PRL release was undetectable in two adenomas. In the other five, hGRF stimulated PRL release and the response was dose related. Furthermore, the PRL response was significantly correlated with the GH response to hGRF. When cells were perfused with somatostatin (1 nM), GH and PRL secretion induced by hGRF was completely antagonized. We also evaluated the effect of hGRF pretreatment on the subsequent GH response to hGRF in two adenomas. hGRF pretreatment (1 nM) for 210 min reduced the GH response to a subsequent hGRF challenge (100 nM) in one tumour but not in the other. In conclusion, the PRL response is similar to the GH response in mixed GH and PRL-secreting adenomas after exposure to GH release-stimulating and inhibiting hormones. After prolonged exposure to hGRF, some adenomas remain responsive to further stimulation with hGRF, whereas others do not.