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The secondary prevention of colorectal cancer is based on the early detection of noninvasive cancer and removal of adenomatous polyps. The two commonly used screening tests are flexible sigmoidoscopy and guaiac fecal occult blood testing. Both were performed simultaneously and independently on 1176 asymptomatic volunteers followed by colonoscopic examination if either occult blood or a neoplasm was detected. Neoplasia (adenomatous polyps or cancer) were found in 48 screenees. Only ten had positive stool occult blood while 45 were detected by sigmoidoscopy. Analysis of sensitivity for neoplasia was 93.8% for sigmoidoscopy but only 20.8% for the occult blood tests, while the positive predictive values for neoplasia were 100% and 23.8% respectively. The fecal occult blood test detected only 18% of screenees with adenomas and 60% with invasive cancer. Flexible sigmoidoscopy detected 95% and 80% respectively. Analysis (kappa statistic) demonstrated little agreement between the two tests (P greater than 0.05), indicating that they are diagnosing different neoplasia. Evaluation of expected gain in diagnosing neoplasia, by combining both tests, gave 18% for the fecal blood test and 94% for the endoscopic test. These results confirm the complementary value of performing both tests, but especially the high sensitivity and predictive value positive of flexible sigmoidoscopy for adenomas, including those with severe dysplasia, and the converse for the fecal occult blood test. This latter test must be recommended and used within a screening program with caution and full understanding of its limitations.