The authors obtained neurological assessments and psychiatric family history data for 40 children with autistic spectrum disorders (autism, Asperger syndrome and pervasive developmental disorder). Neurological evaluation included EEG, MRI, karyotyping and positron emission tomography as indicated. Family history data were obtained from family members during long-term follow-up. 20 probands had positive neurological findings, 18 with negative family history. 14 had no neurological findings and positive family histories; they tended to have higher function. Six had neither, and two had both. The segregation of neurological findings and familial affective disorder was highly significant. These findings suggest that an important subgroup of autistic spectrum disorders may be related etiologically to familial major affective disorders, and may represent the early-life onset of a severe phenotype of major affective, particularly bipolar, disease.