The prefrontal cortex (PFC), defined as the cortical region which has the major reciprocal connections with the mediodorsal thalamic nucleus (MD), has often been implicated in schizophrenia. Morphometric studies have shown altered neuronal density and structure in parts of the PFC in schizophrenic brains. In addition, the MD and nucleus accumbens have shown a significant deficit in total neuron number. The purpose of the present study was to estimate the total neuron number in the PFC in schizophrenics and controls. Using a stereological design, the PFC was studied in eight brains from schizophrenic patients and 10 age-matched control brains. The bilateral average total number of neurons in the PFC was estimated to be 2.76 x 10(9) (CV=S.D./mean=0.15) in the schizophrenic brains whereas that of controls was a non-significantly different value of 3.11 x 10(9) (CV=0.22; P=0.23). Furthermore, no significant differences were found between the two groups in neuronal density (P=0.10) or volume of the PFC (P=0.49). It is of course possible that a neuronal deficit, which cannot be revealed when estimating the total global number of neurons in the whole PFC, might exist in a subregion of the PFC. In conclusion, uniform loss of neuronal soma in the PFC does not appear to constitute the neural substrate of the pathological process in schizophrenia.