Disturbances of the dopaminergic neurotransmitter system have been implicated in the pathogenesis of depressive symptoms. Many studies have, however, failed to detect any association between genetic markers for the dopamine system and mood disorders. A possible reason for this may lie in the definition of phenotype, which is traditionally based on psychiatric diagnosis. In this study, we investigated the possibility that functional variants of the dopamine D4 receptor (DRD4) gene might be associated with depressive symptomatology in a sample of mood disorder subjects. Seventy-nine inpatients affected by bipolar (n=37) and major depressive (n=42) disorder (DSM-IV) were assessed at admission by the Hamilton Depression Rating Scale and were typed for DRD4 variants at the third exon using polymerase chain reaction (PCR) techniques. DRD4 was associated with delusional symptoms (F=5.56; d.f.=2,145; P=0.005), with DRD4*7 exhibiting higher scores when compared to DRD4*4 (P=0.006) variants. Polarity of mood disorder did not influence results significantly. The findings are in accordance with our previous report of an association of the DRD4 gene with delusional symptomatology of major psychoses. DRD4*7 should, therefore, be considered a liability factor for delusional symptoms in mood disorders.