It remains controversial as to what determines the neurodegenerative course in schizophrenia. This study administered a modified version of the Stroop task and investigated the relationship between functional magnetic resonance imaging (fMRI) signal changes in dysfunctioned task-related regions and clinical course variables. Functional MRI data during task performance were acquired from 10 right-handed schizophrenic patients (mean+/-SD age=29.2+/-10.3 years, range of illness duration=0.8-14 years, number of episodes=1-5) and 10 healthy controls (mean+/-SD age=30.3+/-6.4). Imaging data were investigated on a voxel-by-voxel basis for single group analysis and for between-group analysis according to the random effect model using Statistical Parametric Mapping (SPM 99b). Correlation analysis with age as a covariate identified those brain regions whose fMRI signal changes were significantly related to clinical course variables in schizophrenia. The number of psychotic episodes was negatively correlated with the fMRI signal change in the right inferior frontal and the right frontal precentral gyri among the activated regions during the Stroop task in schizophrenia, whereas the length of illness was not so correlated. The number of psychotic episodes was also negatively correlated with the fMRI signal change in the left paracingulate in which functional activity was diminished in the patients relative to the controls. Our results indicate that recurrent psychotic episodes are related to the neurodegenerative course in some dysfunctional brain regions in schizophrenia.