It has been postulated that the prefrontal cortices of schizophrenic patients have significant alterations in their neuropil space. However, previous results have been contradictory and inconclusive, reporting both decreases and increases in the prefrontal neuropil. The present study re-examines these findings based on measurements of cell density, and inter-cellular distances within and between cell minicolumns. The results indicate alterations in the neuropil of schizophrenic patients according to both the lamina and cortical area examined. Alterations were present in all cortical areas studied. The findings suggest an alteration in the modulatory systems innervating the cell minicolumn. Furthermore, the lack of variation in core columnarity parameters argues in favor of a defect post-dating the formation of the cell minicolumn.