Siblings of colorectal cancer patients are estimated to be three times more likely to develop colorectal cancer. Although these high-risk siblings are appropriate candidates for colon cancer screening, the factors that affect their participation in screening programs are not known. A study was conducted to examine the factors that might influence participation in fecal occult blood test (FOBT) screening by high-risk siblings of recently diagnosed colon cancer patients and nonhigh-risk control siblings. Siblings were mailed a sample FOBT card, a letter informing them of their risk status, and an invitation to participate in the FOBT screening program. They were later interviewed by telephone about their intention to participate in FOBT screening. FOBT cards were returned by 52.2% of high-risk siblings compared with 37.7% of control siblings (P less than 0.005). Only 24.8% of the cancer siblings thought they were more likely to get colon cancer compared with others their own age, and 27.8% thought they were less likely. Perceived risk of cancer and demographic and health-related factors did not predict compliance beyond membership in the high-risk group. Siblings of colon cancer patients are more likely to participate in screening, and efforts to screen them could have a substantial impact on colorectal cancer. More work is needed to identify the factors responsible for compliance so that effective interventions can be developed.