Suicidal behavior has been linked to a deficiency in serotonin neurotransmission, but it is not known which brain regions are involved. We determined the pattern of alteration in serotonin 5-HT2 (5-HT2) receptor binding sites in suicide victims in prefrontal cortex compared with temporal cortex using a matched-pairs design to study 11 suicide victims and 11 matched controls, by both membrane binding and quantitative receptor autoradiography. Since a relationship between the serotonergic and noradrenergic systems has been proposed, we also examined beta-adrenergic receptor binding sites. Binding to 5-HT2 and beta-adrenergic sites in slide-mounted sections correlated strongly with binding site number in membrane preparations. A specific laminar distribution of 5-HT2 binding sites was found in both the control and suicide groups, whereas beta-adrenergic binding sites did not differ across cortical layers. A significant increase was found in suicide victims across all cortical layers in both receptor subpopulations in the prefrontal cortex, but only beta-adrenergic sites were increased in the temporal cortex. We conclude that suicide is associated with a localized increase in 5-HT2 binding sites.