A technique of passive hemagglutination inhibition (PHI) has been used to monitor levels of carcinoembryonic antigen (CEA) in human sera following surgical therapy. CEA was coupled to human type O-negative erythrocytes in the presence of bis-diazotized benzidine. Pre-operative and post-operative sera from 11 patients with primary adenocarcinomas of the gastrointestinal tract and from one patient with ulcerative colitis were then tested for their capacity to inhibit the agglutination of the sensitized cells in the presence of a predetermined amount of goat anti-CEA serum. Positive sera were defined as those which inhibited agglutination at dilutions of greater than 1:8. The pre-operative sera from 11 of the 12 patients inhibited agglutination at dilutions of 1:16 or greater. The one negative serum was from a patient with primary adenocarcinoma of the colon in the stage of Dukes' C. At one month post-resection, the PHI titer of six patients with colon cancer and of the patient with ulcerative colitis was less than or equal to 1:8. However, by 4 months post-resection, all but 3 of the patients had PHI titers in the positive range. These elevated titers were accompanied by recurrence of tumor growth and/or metastatic dissemination. A radioimmunoassay was used to quantitate CEA in 22 of the sera which had been tested by PHI. When positive sera were defined as those which inhibited agglutination at dilutions of greater than 1:8 and contained CEA in excess of 5 ng per ml, the results of the two procedures were in agreement for 17 of the 22 specimens. Five sera, representative of 2 patients with colon cancer, were false negative by PHI.