Using a prospectively acquired database of 290 patients with advanced gastric adenocarcinoma, the prognostic significance of serum levels of carcinoembryonic antigen (CEA) (237 patients), alphafeto protein (AFP) (164 patients), beta-human chorionic gonadotrophin (beta HCG) (165 patients), CA19-9 (64 patients) and CA125 (104 patients) and tissue staining for C-erb B-2 (160 patients) and beta HCG (160 patients) was investigated. Serum was taken prior to 5-fluorouracil (5FU)-based chemotherapy and immunohistochemistry was performed on diagnostic specimens. In the univariate analysis, tumour markers of poor prognosis were CEA > or = 5 micrograms/l (P = 0.01; median survival (MS) 42 versus 35 weeks), serum beta HCG > or = 4 U/l (P = 0.02; MS 42 versus 25 weeks), CA125 > or = 35 U/ml (P = 0.03; MS 43 versus 31 weeks) and CA125 > or = 350 U/ml (P = 0.001; MS 42 versus 17 weeks). Other significant factors were poor performance status, the presence of metastases and poorly differentiated tumour histology. Tumours markers of poor prognosis in the multivariate analysis were serum beta HCG > or = 4 IU/l [hazard ratio (HR) 1.7; 95% confidence interval (CI) 2.8-1.1] and CA125 > or = 350 U/ml (HR 2.2; CI 4.2-1.2). There was a degree of subgroup variability in this model but, in general, other factors correlating with a poor survival were poor performance status, metastases and poorly differentiated tumour histology. This is the largest prognostic study of each tumour marker in advanced disease and demonstrates that serum beta HCG and CA125 in gastric cancer prior to chemotherapy do convey an independent poor prognosis which may reflect not just tumour burden but aggressive biology.