Chapter 1 reviews literature, including a systematic and quantitative review of the volumetric MRI studies to date, and examines the links between such biological findings and the clinical features of the illness. Chapter 2 describes an original piece of research designed to examine the biological associations of treatment response in schizophrenia with MRI, SPET and detailed neuropsychological testing. Forty patients were selected as treatment responsive or resistant using standardised criteria. A quantitative analysis of particular regional volumes on MRI revealed that the treatment resistant group had a consistent, but not statistically significant, tendency to smaller cerebral structures. Qualitative ratings showed a tendency to greater atrophy in the treatment resistant patients. The forty SPET scans were subsequently used in a comparison of rCBF in medicated and unmedicated schizophrenia, other psychotic patients and normal controls. The schizophrenic patients showed the predicted hypofrontality, but this was limited to the anterior cingulate and medial pre-frontal cortex. Given some evidence, from post-mortem studies, of a preferential loss of gaba-ergic neurones in the anterior cingulate in schizophrenia, with a compensatory upregulation of non-specific GABA-A receptor binding, a study of GABA receptor binding on SPET was conducted using the benzodiazepine ligand Iomazenil. As described in Chapter 3, the expectation was that Iomazenil binding would be increased in frontal regions, but this was not confirmed in a comparison of ten schizophrenics and ten normal controls; and an apparent reduction of subcortical receptor binding was attributed to methodological problems. Finally, Chapter 4 describes the likely technical and experimental developments in brain imaging studies of schizophrenia in the foreseeable future. Some recommendations are made, based on these advances and the studies described in the thesis, that would help to exploit the full potential of neuroimaging to improve understanding of the pathophysiology of schizophrenia.