The striatum processes motor, cognitive, and limbic function, all of which are perturbed in schizophrenia. The present study examined the synaptic organization of the caudate and putamen in schizophrenia. Postmortem striatum was obtained from 10 normal controls (NC) and 17 subjects with schizophrenia (SZ), prepared for electron microscopy, and analyzed using stereological principles. The densities of total synapses, asymmetric synapses (characteristic of excitatory inputs), and asymmetric axospinous synapses (characteristic of cortical input) were higher in the caudate of the SZs vs. NCs. These changes were most profound in the off-drug SZ cases and were also elevated in subjects on antipsychotic drugs (APDs). In comparison to NCs, there were no significant differences in the putamen of the SZ cohort as a whole group; however, there were more asymmetric axospinous synapses in the off-drug subgroup. The increase in density of synapses in the SZs does not appear to be caused by antipsychotic medication and may represent failure of normal synaptic pruning or abnormal sprouting. Higher density of cortical-type synapses in SZs vs. NCs may reflect adaptation of corticostriatal circuitry or hyperstimulation of striatal projection neurons. The abnormal synaptic organization could have several important and different downstream effects depending on the precise circuitry involved and may be related to limbic or cognitive dysfunction in schizophrenia. Synapse 56:185–197, 2005. © 2005 Wiley-Liss, Inc.