Four mouse monoclonal antibodies to widely distributed human cell surface antigens are described. The AJ2 antigen is one of the immunodominant antigens in mice immunized with human cells, as demonstrated by testing conventional mouse antisera. This antigen has four subunits having molecular weights (MW) of 170 kD, 140 kD, 140 kD, and 28 kD when immunoprecipitated from the immunizing cell line, an astrocytoma. With other cell lines the molecular weights and subunit composition varies, but the major component is always of MW 125-140 kD. The antigen was detected on all human tissue culture cells and on sections of all normal human tissues tested. Antibody MA99 detects the same antigenic complex but shows a slightly different pattern of reactivity with cell lines and tissues. The MA103 antigen has a similar ubiquitous distribution. It is a glycoprotein of MW 50-55 kD and the determinant detected is not denatured by treatment at 100 degrees C. MH99, the third common antigen detected, has two glycosylated subunits with MW of 29 kD and 38 kD. It is present on a subpopulation of tumor cell lines of most histologic types except that it is absent or weakly expressed on melanomas and astrocytomas. MH99 is present on some T lymphomas and leukemias and myeloid leukemias but was not detected on B lymphomas, null cell lymphomas and myelomas. It was detected preferentially on epithelial cells in tissue sections.