OBJECTIVE:To investigate the effect of lithium, anticonvulsants and antipsychotics on brain structure in bipolar disorder (BD). METHOD:A cross-sectional structural brain magnetic resonance imaging study of 74 remitted patients with BD, aged 18-65, who were receiving long-term prophylactic treatment with lithium or anticonvulsants or antipsychotics. Global and regional grey matter, white matter, and cerebrospinal fluid volumes were compared between treatment groups. RESULTS:Grey matter in the subgenual anterior cingulate gyrus on the right (extending into the hypothalamus) and in the postcentral gyrus, the hippocampus/amygdale complex and the insula on the left was greater in BD patients on lithium treatment compared to all other treatment groups. CONCLUSION:Lithium treatment in BD has a significant effect on brain structure particularly in limbic/paralimbic regions associated with emotional processing.