Regional 5-hydroxytryptamine(1A) (5-HT(1A)) receptor binding potential (BP) of depressed subjects with primary, recurrent, familial mood disorders was compared to that of healthy controls by using positron emission tomography and [carbonyl-(11)C]WAY-100635 ¿[(11)C]N-(2-(4-(2-methoxyphenyl)-1-piperazin-1-yl)ethyl)-N-(2- pyridy l)cyclohexanecarboxamide¿. The mean 5-HT(1A) receptor BP was reduced 42% in the midbrain raphe and 25-33% in limbic and neocortical areas in the mesiotemporal, occipital, and parietal cortex. The magnitude of these abnormalities was most prominent in bipolar depressives and unipolar depressives who had bipolar relatives. These abnormal reductions in 5-HT(1A) receptor BP are consistent with in vivo evidence that 5-HT(1A) receptor sensitivity is reduced in major depressive disorder and postmortem data showing a widespread deficit of 5-HT(1A) receptor expression in primary mood disorders.