Non-specific cross-reacting antigens (NCA-95 = CD66b and NCA-50/90 = CD66c) are members of the CEA (carcinoembryonic antigen = CD66e) family. Analysis of mRNA levels of CD66c in colon tumors suggests that this antigen is strongly up-regulated compared to its normal counterpart and could, therefore, be of clinical interest. CD66c is also expressed in normal lung and spleen tissues and, above all, on granulocytes. The appearance of CD66b in serum, the only strictly granulocyte-specific antigen, could point to the involvement of granulocytes in disease. Specific sandwich ELISAs have been established to determine CEA, CD66b and CD66c levels in serum. Controls have been carried out by testing sera from patients with benign tumors or inflammatory diseases and from healthy individuals. In sera of most patients suffering from solid tumors, sensitivities for CD66c are comparable to or lower than those for CEA. CD66c showed a much higher sensitivity in early colon tumor stages. Sensitivities over 40% have been determined for CD66b in sera of patients with uterine and kidney carcinomas. CML patients revealed sensitivities of 84% for CD66c and 47% for CD66b. Investigations of sera from patients with inflammatory colon diseases which are negative for CEA showed high sensitivity for CD66c but not for the granulocyte-specific CD66b. Patients with mastopathy revealed sensitivities of over 40% for both CD66c and CD66b. CD66b, CD66c and CEA are independently regulated proteins in a high percentage of patients. The simultaneous determination of CEA and CD66b/c can increase the sensitivities for malignant tumors but high sensitivities of CD66b/c for benign diseases limit their usefulness as tumor markers. CD66b may be interesting as a marker for kidney and corpus carcinomas, for which good markers are not yet available.