We screened groups at high risk for colorectal neoplasms, determining the efficacy of the leukocyte adherence inhibition test (LAI) for early detection, in comparison with that of the fecal occult blood (Hemoccult) test and sigmoidoscopy or colonoscopy. Those screened included 549 first-degree relatives of patients with colorectal cancer, 190 patients with a past history of colorectal adenoma or carcinoma and 67 with a past history of breast or gynecological cancer or inflammatory bowel disease. 146 normal volunteers served as controls. In 782 of those fully screened during a 3-year period, 121 had adenomas (15.5%) and 5 had invasive cancer (0.6%). The LAI test was positive in 21% of those at high risk and in 7.5% of the controls. The hemoccult test was positive in only 4.8%, but in 1/3 of them neoplasms were found. This predictive value of 33% compares with only 16% for the LAI test. That most of the neoplasms found were adenomas and not invasive cancer may be due to the relative youth of most of those screened. We conclude that the groups studied were indeed at high risk. The LAI test is not sensitive enough to identify benign adenomas but might serve as another risk-market for colorectal neoplasms. Long-term follow-up of those at high-risk with positive LAI tests may prove that we have identified a subgroup truly at risk.