Restriction fragment-length polymorphisms in the chromosome 5q21-22 region can now be used clinically for premorbid diagnosis and counseling in familial adenomatous polyposis. Two families are presented in which DNA diagnosis for familial adenomatous polyposis was performed using linked restriction fragment-length polymorphisms. Screening guidelines are improved using data from the polyposis registers at St. Mark's Hospital (London) and Western Australia (Perth) on at-risk family members who subsequently developed familial adenomatous polyposis. In these registers, 103 of 137 relatives tested positive on initial screening; of the remaining 34, the average interval between initial negative screening and development of familial adenomatous polyposis was 7.5 years. All those who had inherited the familial adenomatous polyposis gene manifested the polyps by age 34 years. Combined with linkage marker data, the a priori 50% risk for relatives can now be reduced to less than 0.5% by age 30 years if there is an initial negative result on sigmoidoscopy and a negative diagnosis by linkage analysis. The screening management for those found by linkage to have inherited familial adenomatous polyposis remains unchanged from established recommendations; however, for individuals who most likely have not inherited familial adenomatous polyposis, the clinician can emphasize the positive aspects of screening management, including longer screening intervals.