Several pieces of evidence are consistent with the involvement of dopamine neurotransmission in the aetiology of bipolar disorder. We have tested the hypothesis that the functional mutation Ser311-->Cys of the dopamine D2 receptor gene confers susceptibility to bipolar disorder. There was no increased frequency of the mutation in 82 bipolar probands compared with 72 controls, showing that this mutation is not involved in the pathogenesis of (at least) the vast majority of cases of bipolar disorder. Our findings are consistent with other evidence from linkage and association studies against the involvement of the dopamine D2 receptor in bipolar disorder.