Although the incidence of bipolar disorder rivals that of schizophrenia, there has been relatively little exploration of the underlying pathology of the disorder using postmortem studies. More recently, however, the focus on bipolar disorder and, therefore, its underlying pathology has intensified, stimulating new areas of research. In part, this may have been triggered by the improved clinical outcomes obtained using atypical antipsychotics as an adjunctive therapy to mood stabilizers (Yatham Bipolar Disord 2003, 5 7–19), reawakening interest in neurotransmitter dysfunction as a potential basis of the disorder. Morphological studies indicate that there is an apparent disruption in cortical neuronal/glial balance in subjects with bipolar disorder (Rajkowska et al. Biol Psychiatry 2001, 49 741–752; Cotter et al. Cereb Cortex 2002, 12 386–394). Furthermore, impaired executive function suggests that functionality of the dorsolateral prefrontal cortex may be compromised (Martinez-Aran et al. Psychother and Psychosom 2002, 71 39–46). Studies in our laboratory have shown that in the dorsolateral prefrontal cortex, Brodmann's area 9, there is little sign of alterations in neurotransmission as defined by receptor number. However, there are quite profound changes in some of the molecules involved in mediating normal synaptic function. Together, these data suggest that the functionality of this brain region may be disrupted in bipolar disorder.