The genetic basis for colorectal cancer was investigated by complex segregation analysis of a published series of 305 pedigrees ascertained through a large population database. Two hundred and five of the pedigrees were ascertained through patients diagnosed with colorectal cancer before age 55, and 100 from patients diagnosed with colorectal cancer between the ages of 55 and 74. The analysis was carried out using the program POINTER. Using the joint-likelihood approach, the familial aggregation of colorectal cancer was compatible with the inheritance of a dominant gene. The gene frequency of the putative abnormal allele was 0.002 with a lifetime penetrance of 85%. However, under conditional likelihood, this mode of inheritance for a major gene was not favoured. The possible aetiologies of this paradoxical finding are discussed.