A gene associated with the inherited syndrome, familial adenomatous polyposis (FAP), has been localized to the long arm of chromosome 5 near the 5q21-22 region, and markers that identify genetic polymorphisms near this locus are now available. The authors evaluated several of these markers for linkage to the FAP trait in 11 families entered in the Cleveland Clinic Polyposis Registry. The original probe that established linkage to the FAP locus (C11p11) has limited utility for family studies because of low heterozygosity and distance from the FAP gene. Other probes, however, should be useful for assessing FAP inheritance by restriction fragment length polymorphism analysis, for presymptomatic diagnosis of the disease.