Plasma specimens assessed for carcinoembryonic antigen (CEA) in the clinical laboratory for the detection of colorectal cancer were simultaneously assayed in our laboratory for α-1-acid glycoprotein (α1AG), by means of a solid-phase enzyme-linked immunosorbent assay we developed. In 28 patients with colorectal cancer of Dukes A, B, and C classes, elevated levels of α1AG were seen in 12 and of CEA in 8. In 44 patients with distant metastasis (Dukes D lesions), elevated plasma levels of α1AG were seen in 29 and of CEA in 34. No statistical differences in the detection rate were found among these markers in these 2 groups of patients. In 33 cases of non-neoplastic disease involving the large bowel, elevated plasma levels of α1AG were seen in 6, and elevated CEA levels were seen in 7. There was no statistical difference of false positive rates among these two markers. Elevated plasma levels of either CEA or α1AG were found in 57 cases of colorectal cancer. This preliminary study suggests that the sensitivity of the plasma α1AG assay is similar to that of the CEA assay in the detection of colorectal cancer. The combination of these two assays increases the detection rate of colorectal cancer significantly.