Asperger syndrome (AS) is a childhood-onset disorder often described as a mild variant of autism. Although classified as a distinct disorder in the DSM-IV, its overlap with autism continues to be a matter of ongoing debate. While the family genetic origins of autism are well established, few studies have investigated this topic in AS using current operational criteria. In this report, we examined the family psychiatric history of 58 subjects with AS diagnosed according to DSM-IV criteria (48 males; mean age 13.34; mean full scale IQ 104.87). All subjects had a history of mild autistic social deficits; focused special interests; normal level of intelligence; and an odd and often pedantic manner of speaking. None had a previous diagnosis of autism. Of the 58 subjects with Asperger syndrome, three had first degree relatives with AS; nine (15%) had a family history of schizophrenia; and 35 (60%) had a family history of depression. Of the 64 siblings, four had a diagnosis of AS and none of autism. Compared with a group of 39 subjects with normal intelligence autism (high functioning autism, HFA; 33 males; mean age 15.34; mean full scale IQ 85.89) subjects with AS were more likely to have relatives with depression; schizophrenia; and the broader autistic phenotype. Possible reasons for and implications of these findings are discussed.