While the changes in the volume of the temporal lobe and its sub-regions over the course of illness have been studied in patients with schizophrenia, few studies have examined changes in the frontal lobe between the first episode and the chronic stage. In this study, we focussed on the effect of illness stage and duration of illness on the volume of frontal lobe regions, though we also examined several other regions to establish the specificity of any effects, if observed, in this region. We compared the volumes of brain regions among 34 first-episode schizophrenia patients, 49 chronic schizophrenia patients, 18 healthy controls matched, on average, to the first-episode patients and 21 healthy controls matched, on average, to the chronic patients. Logarithmic regression analyses examined the relationships between the duration of illness and the brain regional volumes in the patient group. The results showed that chronic patients had smaller prefrontal cortical grey matter volumes, but larger premotor cortical and putamen volumes compared to first-episode patients and matched healthy controls. Although there were significant patient-by-control group interactions in the cerebellum and sensori-motor cortical grey matter volumes, these did not survive correction for multiple comparisons. There was a significant exponential relation between the duration of illness and the volumes of prefrontal cortex, parieto-occipital cortex grey matter, thalamus and putamen, suggesting that these regions are susceptible to change as the disorder persists. The enlargement of the premotor cortex and putamen are likely to be a result of antipsychotic medication.