We studied differences in the number and morphology of parvalbumin-immunoreactive (PV-IR) interneurons in 43 hippocampal specimens from patients with classical Ammon's horn sclerosis (AHS) who underwent anterior temporal lobectomy, as compared with 14 autopsy and non-AHS surgical control specimens. PV-IR neuronal loss in the AHS specimens varied significantly from that expected based on overall AHS-associated pyramidal and granule neuron loss. Most striking was the loss of PV-IR interneurons in CA4 of the AHS specimens, which was 12 times greater than AHS-associated pyramidal neuron loss, and significantly exceeded the PV-IR interneuron loss observed in the other sectors of the hippocampus. In addition, the PV-IR interneurons in the AHS specimens had markedly smaller and less defined cell bodies and shortened and simplified dendritic arbors compared with the PV-IR interneurons in the control specimens. Other differences noted in the AHS specimens included prominent dendritic varicosities; the loss or interruption of a band formed by PV-IR terminals in the dentate gyrus; and the virtual absence of a small, intensely staining PV-IR interneuron with a short, exuberant dendritic arbor that was readily identified in the autopsy specimens. We discuss these findings in relationship to the development of classical AHS and complex partial seizures (CPS).