The role of the dopaminergic system in P300 has been implicated and previous studies have suggested the presence of a heritable component in the genesis of P300 or P3, a late positive component of the event-related potential. In the present investigation, 155 Caucasian male and female diagnosed neuropsychiatrically-ill patients with and without comorbid drug and alcohol abuse/dependence were genotyped for the presence or absence of the A1 allele of the D2 dopamine receptor gene (DRD2). The relationship of the A1 and A2 alleles to P3 amplitude and latency was also determined. The results showed no significant difference in P3 amplitude between all groups studied with A1 and A2 allele carriers. However, we now report prolonged P3 latency in neuropsychiatrically-ill patients (with or without polysubstance abuse) with those carrying two copies of the A1 allele (homozygote) of the DRD2 gene (quadratic trend, p = 0.01). Moreover, the age-adjusted mean P3 latency in the D2A2/A2 allele group was 327.8 +/- 3.08 ms compared by ANOVA, to 360.04 +/- 4.86 ms in the D2A1/A1 group. Our work suggests an association of polymorphisms of the DRD2 gene and a biological marker previously indicated to have predictive value in vulnerability to substance abuse.