The presence of growth factors and their receptors in human midgut carcinoids and in gastric carcinoids of Mastomys have been investigated. Human midgut carcinoid tumours produce IGF-I as demonstrated by immunocytochemistry and radioimmunoassay. IGF-I receptors were detectable in half of the tumours and stimulation of cultured tumour cells with IGF-I enhanced DNA synthesis. IGF-I may therefore act as an autocrine stimulator of carcinoid tumour growth. Expression of TGF-alpha and EGF-receptors could also be demonstrated in midgut carcinoids by immunocytochemistry and Northern analysis, suggesting that TGF-alpha participates in the autocrine modulation of carcinoid growth. Co-culture of human midgut carcinoid tumours and rat fetal cholinergic neurons demonstrated secretion of a potent neuronotrophic factor by cultured tumour cells. IGF-I and TGF-alpha may account for these neuronotrophic effects, but carcinoid tumours may also secrete an as yet unidentified growth factor. Gastric (ECL cell) carcinoids developed rapidly in Mastomys during hypergastrinemia due to histamine2-receptor blockade, suggesting that gastrin is an essential growth factor for these carcinoids.