The pathogenesis of psoriasis is not fully understood, but population and twin studies suggest a large heritable component to the etiology. Several large population studies have also suggested a parental sex effect. Since 1994, three main genetic loci (on chromosomes 17q, 4q, and 6p) have been reported in genome scans. With a view to elucidating the genetic basis of psoriasis, we have carried out linkage analysis in a large number of families with well-characterized psoriasis. From a cohort of 1250 probands with psoriasis, 395 individuals (301 affected, 94 unaffected) in 103 families were recruited. Each subject was carefully examined by an experienced dermatologist and stringent diagnostic criteria applied. Genotypes were generated at 11 polymorphic loci on chromosomes 17q, 4q, and 6p and the results were analyzed parametrically and nonparametrically. In the population from which the probands were drawn, there was evidence of a parental sex effect, more probands having an affected father than an affected mother. Genetic anticipation was also apparent and most marked if the disease was inherited from the father. The loci on chromosomes 17 and 4 were not replicated but there was strong evidence for linkage to chromosome 6p (maximum two point LOD score 4.63 at D6S291). The evidence for linkage in sibling pair analysis was greatest when the allele was of paternal origin and was most significant in those families without psoriatic arthritis. These studies confirm the presence of a susceptibility gene on chromosome 6p. The available evidence suggests that a different genetic susceptibility may underlie psoriasis and psoriatic arthritis.