Several studies have suggested a role for the histocompatibility complex of loci (HLA) in the genetic susceptibility to autism. We have tested this hypothesis by linkage analysis using genetic marker loci in the HLA region on chromosome 6p in multiplex families with autism. We have examined sharing of alleles identical by descent in 97 affected sib pairs from 90 families. Results demonstrate no deviation from the null expectation of 50% sharing of alleles in this region; in fact, for most marker loci, the observed sharing was less than 50%. Thus, it is unlikely that loci in this region contribute to the genetic etiology of autism to any significant extent in our families.