Primary and metastatic tumor tissues from 21 patients with ovarian epithelial cancer were studied with a panel of 8 monoclonal antibodies. Primary tumors reacted with 1 to 7 antibodies (mean, 3.5). Heterogeneity was observed even within histologic subtypes. Comparison of metastases (including ascites) with their respective primaries revealed differences in antigen profile in each of 10 cases studied. In one patient variable antigen expression was observed in five ascites samples collected over a 12-month period. These observations of antigenic heterogeneity and modulation with respect to site and time suggest that single monoclonal antibody immunotherapy would not be appropriate for all patients or even for a single patient over time.