Linkage and association studies implicate the dopamine transporter gene (DAT1) in the etiopathophysiology of bipolar disorder. We have recently reported the association between the DAT1 core promoter -67A/T polymorphism and this disorder in a sample of Iranian patients. For the first time, these data support sex dimorphism in the homozygosity for the -67 T-allele between male and female affected cases. The present study was undertaken with a larger sample size of cases (N=240) and controls (N=213) to determine whether there is consistent difference between male and female patients and homozygosity for this allele. The results confirm and strengthen our preliminary observation that homozygosity for the T-allele is a predisposing factor in male patients, but not in females (chi2=8.825, df=1, p=0.003). Moreover, Hardy-Weinberg disequilibrium was observed in the female cases studied (chi2=12.9, df=1, p=0.0003), which may reflect the underlying biology. These findings imply gender dimorphism with respect to the DAT1 -67 alleles and susceptibility to disease.