Turcot syndrome (TS) is a rare genetic disease in which brain tumors occur in association with colonic polyposis. Since Turcot's original description in 1959, there have been disagreements about the mode of inheritance as well as the clinical expression of this condition. Some investigators maintain that TS is a phenotypic variant of the autosomal dominant familial adenomatous polyposis (FAP), while others observe that there are clinical differences between TS and FAP, and that the pattern of inheritance of TS is autosomal recessive. The distribution of persons with colonic lesions in a family with a patient of colonic polyposis and a brain tumor, described in this report, favored the recessive hypothesis. In this family, the involvement of the FAP gene on chromosome 5q21-q22 could be excluded by a linkage study using a panel of FAP-linked DNA markers. This finding, which indicates the occurrence of another polyposis gene elsewhere in the genome, will have consequences for the presymptomatic diagnosis of FAP by linked DNA markers. We conclude that TS is a distinct clinical-genetical entity with the triad of atypical polyposis coli, CNS tumors, and a recessive mode of inheritance.