Transforming growth factor-alpha (TGF-alpha) is a ligand for epidermal growth factor receptor (EGFR) and it is overexpressed in various malignancies including lung, esophageal, colorectal, ovarian and gastric carcinomas. In patients with gastric carcinoma, its overexpression may be associated with advanced stage or poor prognosis. We have recently demonstrated that the mean serum level for EGFR in gastric carcinoma patients was significantly elevated compared with that of healthy controls. Using the enzyme-linked immunosorbent assay, the levels of TGF-alpha were determined in serum from 40 patients with gastric carcinoma (5 patients with stage I, 2 stage II, 4 stage III, and 29 stage IV patients) and 33 healthy controls. The mean serum level for TGF-alpha in the gastric carcinoma patients was significantly elevated as compared with that of healthy controls (104 +/- 235 vs. 22 +/- 16 pg/ml; p = 0.03). Eleven patients with gastric carcinoma (27.5%) showed elevated serum TGF-alpha levels above the cutoff value of 54 pg/ml (defined as 2 standard deviations above the mean of the control group). No significant association was noted between the positivity of TGF-alpha and clinicopathologic characteristics including gender, age and stage. However, poorly differentiated adenocarcinoma showed a higher positivity of serum TGF-alpha (43.8%) compared with other histologic types, which was marginally significant (p = 0.06). These results suggest that serum TGF-alpha could be useful as a tumor marker of gastric carcinoma for predicting prognosis and follow-up after surgery in patients whose initial serum TGF-alpha levels are elevated.