Five rat monoclonal antibodies to human uveal melanoma were produced using primary tumor tissue for immunization and screening. These monoclonal antibodies were tested by enzyme-linked immunosorbent assay against 12 uveal melanomas, one breast carcinoma, and peripheral blood lymphocytes from five healthy volunteers. One monoclonal antibody, 4A3, reacted against all the melanomas and none of the controls. On immunoblotting, this monoclonal antibody identified a protein doublet in the molecular weight range 55,000. With these monoclonal antibodies, it was possible to demonstrate significant variation in the antigenic profiles of the uveal melanomas which was not present in the controls.