Several studies have pointed to alterations in mean volumes, neuron densities and total neuron numbers in the caudate nucleus (CN), putamen, nucleus accumbens (NA), mediodorsal nucleus of the thalamus (MDNT) and lateral nucleus of the amygdala (LNA) in schizophrenia. However, the results of these studies are conflicting and no clear pattern of alterations has yet been established in these subcortical regions, possibly due to differences in quantitative histological methods used as well as differences in the investigated case series. The present study investigates these subcortical regions in both hemispheres of the same post-mortem brains for volume, neuron density and total neuron number with high-precision design-based stereology. The analysed case series consisted of 13 post-mortem brains from male schizophrenic patients [age range: 22-64 years; mean age 51.5 +/- 3.3 years (mean +/- SEM)] and 13 age-matched male controls (age range: 25-65 years; mean age 51.9 +/- 3.1 years). A general linear model multivariate analysis of variance with diagnosis and hemisphere as fixed factors and illness duration (schizophrenic patients) or age (controls), post-mortem interval and fixation time as covariates showed a number of statistically significant alterations in the brains from schizophrenic patients compared with the controls. There was a reduced mean volume of the putamen [-5.0% on the left side (l) and -4.1% on the right side (r)] and the LNA (l: -12.1%, r: -17.6%), and a reduced mean total neuron number in the CN (l: -10.4%, r: -10.2%), putamen (l: -8.1%, r: -11.6%) and the LNA (l: -15.9%, r: -16.2%). These data show a previously unreported, distinct pattern of alterations in mean total neuron numbers in identified subcortical brain regions in a carefully selected sample of brains from schizophrenic patients. The rigorous quantitative analysis of several regions in brains from schizophrenic patients and matched controls is crucial to provide reliable information on the neuropathology of schizophrenia as well as insights about its pathogenesis.