Inhibition mediated by gamma-aminobutyric acid at the axon initial segment of pyramidal neurons appears to be altered in the prefrontal cortex in schizophrenia. This study examined the densities and laminar distribution of axon initial segments labeled with an antibody against the serotonin(1A) (5-HT(1A)) receptor, which also mediates inhibitory regulation of pyramidal neurons, in subjects with schizophrenia. The densities and laminar distribution of axon initial segments with 5-HT(1A)-like immunoreactivity were assessed in postmortem tissue from the prefrontal cortex (Brodmann's area 46) of 14 matched triads of subjects with schizophrenia, subjects with major depressive disorder, and comparison subjects with no psychiatric disorder. The relative densities of the labeled axon initial segment in both the superficial and the deep cortical layers did not differ across the three subject groups. The findings do not support a role for altered serotonin transmission by means of the 5-HT(1A) receptor in dysfunction of prefrontal cortex pyramidal neurons in schizophrenia.