Several approaches were made to produce new monoclonal antibodies (MoAb) to human colonic tumours using different immunogens, such as colon cell lines, and tissue and serum from patients with colon cancer. Six MoAb were produced but all were found to be reactive with carcino-embryonic antigen (CEA). Through tissue reactivity and competitive inhibition studies it was found that four epitopes could be detected: CEA-1 detected by MoAb I-1 and O-1; CEA-2 detected by MoAb 17C4; CEA-3 detected by MoAb LK-4 and XPX-13 and CEA-4 detected by MoAb JGT-13. CEA-2 was also found on granulocytes and probably detects normal cross-reacting antigen (NCA). In formalin-fixed tissues the CEA-specific epitopes were absent from normal adult tissues, but this was an artefact of the fixation procedure and fresh, non-fixed colonic tissues were clearly reactive. All six MoAb reacted with greater than 70% of colonic tumours when tested by the immunoperoxidase technique and gave different patterns of reactivity reflecting the differential expression of the CEA 1-4 epitopes. Despite the apparent specificity of these MoAb for colon cancer, serum testing using MoAb gave similar results to CEA polyclonal antibodies, that is the MoAb gave no obvious advantage. Thus efforts to produce new reagents to colon cancer yielded only anti-CEA monoclonal reagents. Clearly, other new approaches are required to produce better diagnostic reagents for this common disease.