Abstract The A1 allele of the DRD2/ANKK1 Taq1A polymorphism (rs1800497) is associated with reduced striatal D2/3 receptor binding in healthy individuals (Con) as well as depression and addiction. However, the effect of rs1800497 on D2/3 receptor binding in depressed patients as well as the SNP's effect on D2/3 binding during reward-associated dopamine release is unknown. Twelve unmedicated patients with major depressive disorder (MDD) and 24 Con completed PET scans with [11C]raclopride, once without receiving monetary rewards (baseline) and once while winning money. In Con, the A1 allele was associated with reduced baseline binding potential (BPND) in the middle caudate and ventral striatum. However, in MDD patients the A1 allele was associated with increased baseline BPND in these regions. There were no significant associations between rs1800497 and change in BPND during reward-associated dopamine release. Conceivably, the A1 allele predisposes to depression and addiction via its effect on the post-synaptic D2 receptor.