There are many changes in the properties of cells following malignant transformation. We have recently concentrated on changes in the expression of surface molecules that might represent tumor-specific markers that could be exploited both for diagnosis and therapy of human tumors. Using hybridoma technology and morphologic methods, we have continued to isolate monoclonal antibodies to surface epitopes on human tumor cells. By immunizing mice with MCF-7 cultured human breast tumor cells, we have generated a series of related monoclonal antibodies (B1, B2, B3, K2, K3) to mucin-like materials expressed in adenocarcinomas of breast, colon, stomach and other organs. These antibodies are under evaluation for diagnostic and therapeutic use. Using OVCAR-3 human ovarian cancer cells, we have generated a new antibody, K1, that recognizes a unique epitope on an antigen similar to the CA125 antigen found in ovarian cancer. This new antibody may prove useful for diagnostic screening and perhaps for therapy of ovarian cancer. We have also evaluated an antibody to the external domain of the Neu oncogen product, which may be useful for therapy in selected tumors of breast, ovary or other organs. In other studies, we have begun examining the intracellular distribution of the chemotherapeutic drug daunomycin by a novel electron microscopic approach, and we have also localized a transgene product in mice expressing the human EGF receptor exclusively in testis at specific stages of spermatocyte differentiation.