The new monoclonal antibodies (MoAbs) E401, E811, E907 and E919 were prepared and characterized. These recognized an extracellular domain (amino acids No. 292-370) on the human c-erbB-2 gene product. Utilizing MoAb E811 and MoAb E919, a double determinant immunoassay (DDIA) was established to detect the soluble and the shed forms of the c-erbB-2 molecule. The levels of circulating erbB-2 antigen in the sera of patients with benign diseases and healthy controls were very low. The incidence of positivity for shed c-erbB-2 antigen in gastric cancer, colonic cancer, gall-bladder cancer, pancreatic cancer and other cancers were 7.4%, 4.2%, 0%, 6.7% and 0%, respectively. Four of 54 patients with gastric carcinoma showed high levels of serum c-erbB-2 antigen. They belonged to clinical stage IV and their histological types were all well differentiated adenocarcinomas (two papillary and two tubular adenocarcinomas). Furthermore, the incidence of positive staining in gastric cancer was 34.6%; higher than that for shedding erbB-2 antigen. Most of the cases which showed erbB-2 expression on cells were well-differentiated adenocarcinomas. Meanwhile, the distribution of erbB-2 antigen was limited in normal tissues. The results suggest that the expression of erbB-2 antigen is largely restricted to adenocarcinoma cells. It may not shed easily from these cells, and therefore it may be a very useful target molecule for passive immunotherapy.