Expression of mRNA-encoding transforming growth factors alpha and beta (TGF alpha and beta), epidermal growth factor receptor (EGFR), and platelet-derived growth factors (PDGF) A and B chains was examined in 63 human gastric biopsies. Despite considerable individual variation, transcript levels were generally higher in 16 paired gastric tumors compared with surrounding epithelium. Marked increases were observed for the TGFs and c-sis, whereas EGFR mRNA was poorly expressed; there was no correlation with pathological staging of the cancers. In the nonneoplastic tissues, 14 had normal histology and 27 displayed superficial (SG) or atrophic gastritis (AG). Transcript levels greater than or equal to + were similar between these categories for all the growth factors, but were about 50% higher for EGFR in the tissues with gastritis. Concurrent expression of TGF alpha and EGFR (greater than or equal to + level) was more frequent in the paired tumors (38%) than in adjacent nonmalignant tissue (6%) and was seen in only one of 14 (7%) normal samples, in three of 19 (16%) of those with AG, and none of eight of those displaying SG. High levels of TGF beta and PDGFA mRNA were expressed in gastric ulcers, with little or no TGF alpha and EGFR transcripts; in contrast both TGFs and EGFR message were found in normal oesophagus. Stomach tissues are thus capable of synthesizing a variety of growth factors. These may be associated with nonneoplastic hyperplasia and/or malignant proliferation. Coexpression of TGF alpha/EGFR supports the possibility of an autocrine loop sustaining tumor growth which is different from the mechanisms responsible for normal cellular proliferation.