In previous communications, we have described the expression of class I and class II histocompatibility antigens by hybrids of human B and T lymphoblastoid cell lines (B- and T-LCL). In all cases, such hybrids were found to resemble their B-LCL parents, expressing high levels of class I and class II antigens encoded by both parent cell lines. In the current study, we have conducted a more extensive analysis of B-LCLxT-LCL hybrids with a panel of monoclonal antibodies recognizing a variety of B and T lymphocyte differentiation markers. Rather than exhibiting a B-LCL-dominant phenotype, most hybrids were found to express a majority of both T and B lymphocyte antigens expressed by their parent cell lines. Several hybrids of pairs of dissimilar T-LCL were also produced and analyzed. Again, a majority of parental antigens was expressed on the hybrids. However, eight of eight hybrids of the T-LCL CEM and HSB failed to express HNK-1, an antigen strongly expressed by HSB; and two hybrids of the T-LCL CEM and SKW3 expressed CD3, an antigen expressed by neither parent cell line.