Hérault et al. (1993) previously reported a significant association between autism and the larger fragments of the c-Harvey-Ras (HRAS) Bam H1 polymorphism. We have sought to verify this finding and determine if there was any evidence for an association with other psychiatric disorders. Because of its greater sensitivity, we have examined the HRAS Msp 1 polymorphism. We found a just significant increase in the prevalence of the > 2.1 kb alleles in 48 subjects with autism versus 50 control subjects. There was no increase in the prevalence of the > 2.1 kb alleles in 164 probands with Tourette's syndrome. Examination of 16 preselected symptom clusters, however, showed a significant trend toward higher scores for obsessive-compulsive and phobic symptoms in > 2.1 kb homozygotes. While this locus requires further study, in conjunction with the results of Hérault et al., the present findings suggest that genetic defects in HRAS, and possibly other components of the G protein secondary messenger system, may play a role in some psychiatric disorders.