One hundred seventy-nine primary human gastric tumors not associated with early cancer or noncurative resection were examined immunohistochemically for the expression of c-erbB-2 protein. Positive staining, regarded as an indication of gene amplification, was evident in 22(12%) of the tumors. Of various clinicopathological factors considered, a statistically significant difference in association with frequency of expression was noted only for histological differentiation, as follows: 39% positive staining in papillary, 17% in well differentiated, 5% in moderately differentiated, and 4% in undifferentiated adenocarcinomas (P greater than 0.01). The 5-year survival rates of patients with positive and negative c-erbB-2 staining were 57% and 59%, respectively. These findings indicate that, in the case of human gastric adenocarcinoma, expression of c-erbB-2 protein is correlated with tumor histological differentiation. Our results also suggest that the presence or absence of c-erbB-2 protein may not serve as a prognostic indicator, particularly in cases of adenocarcinoma of the stomach.