Protein tyrosine phosphatases have been implicated in the regulation of serotonergic and dopaminergic activity in the central nervous system. In a recent study we found that nonA/nonA homozygosity at the locus codifying for the low molecular weight protein tyrosine phosphatase (ACP1) was associated with increased rates of major depression in males (P<0.00003), suggesting that the ACP1*A single nucleotide polymorphism (SNP) may be an important marker for psychopathology. In the present study we examined the ACP1*A SNP in 539 screened controls and 184 male Tourette syndrome (TS) cases, all Caucasians of European descent. The frequency of the nonA allele was markedly increased in TS cases relative to controls (P<0.0005), but this difference was restricted to cases with comorbid attention-deficit hyperactivity disorder (P<0.0001) and conduct disorder (P<0.0002), while having little relevance to TS itself.