BACKGROUND The high incidence of and mortality from colorectal cancer (160,000 new cases and 60,000 deaths in the United States each year) are compelling public health concerns. Following the evolution of effective surgery for this disease since the 1960s, the focus has been on improving methods of detection and integrating them into effective screening programs. OBJECTIVE This was the first study to evaluate the effectiveness, in a setting of comprehensive medical examinations, of using the fecal occult blood test in conjunction with sigmoidoscopy, rather than sigmoidoscopy alone, to screen for colorectal cancer. Our end points were extent of compliance with fecal occult blood test and sigmoidoscopy, numbers of cancers detected, and mortality rate. METHODS From 1975 through 1979, a total of 21,756 patients (aged 40 and older) who presented at the Preventive Medicine Institute-Strang Clinic for routine medical examinations were enrolled by calendar period into study and control groups. Study patients were offered annually both rigid sigmoidoscopy examinations and fecal occult blood tests requiring two stool specimens per day for 3 days, while control patients were offered only annual sigmoidoscopy. The majority of fecal occult blood test cards were not rehydrated before assay. Patients with positive tests were referred for double-contrast barium enema and colonoscopy. Two distinct trials were carried out. Trial I was primarily a demonstration of feasibility of using the fecal occult blood test as a supplemental screening method. Of the 9277 participants, 7168 (77%) were assigned to the study group and offered the fecal occult blood test. In trial II, approximately half of the 12,479 patients were assigned to each group. Patients in both trials had follow-up through 1984. RESULTS Compliance with the fecal occult blood test was initially high in both trials, but diminished such that only 56% of study patients in trial I and 20% of those in trial II returned for second tests. On the initial (prevalence) screen, a substantial number of early-stage cancers were detected by the fecal occult blood test, primarily in trial II. In trial II, survival probability was significantly greater (P < .001) in the study group than in the controls (70% versus 48%), and colorectal cancer mortality was lower (0.36 versus 0.63) with borderline significance (P = .053, one-sided). CONCLUSIONS The screening of average-risk individuals (aged 50 and older) for colorectal cancer through use of the fecal occult blood test in conjunction with sigmoidoscopy can increase the likelihood of early detection of this disease. This practice, coupled with prompt diagnostic work-up following positive tests, will result in treatment of earlier stage cancers and increased survival after treatment.