The study of cerebral structural abnormalities is one of the most active and interesting fields of biological psychiatry research. Magnetic Resonance Imaging (MRI) studies have now demonstrated cerebral structural abnormalities relative to cerebral ventricles, temporal lobe, limbic structures, frontal lobe and basal ganglia.Neuromorphological abnormalities have been correlated with symptomatological patterns, neuropsychological performance, premorbid functioning and duration of illness. All of these measures are considered to be predictors of neuroleptic response and outcome of schizophrenia.The relationship of brain morphology to treatment response and clinical outcome of the disease is still a controversial issue, and some methodological questions remain unresolved: the high number of potential correlations between morphological and outcome variables increases the probability of chance findings; the fact that patients showing a more severe psychopathology at the onset of the disease, can lead to the false observations either of a better response, if this is evaluated as the percent of symptoms impovement relative to the baseline, or of a worse response, if evaluated as the reaching of a given threshold.In this paper we report data obtained in one of our recent MRI studies, aimed at investigating the association between neuromorphological variables, quantitatively assessed, and symptomatological course and outcome of schizophrenic patients.A group of 15 schizophrenic subjects (DSM III-R), 9 males and 6 females, mean age 25.6 ± 6.3 years, mean duration of illness 1.6 ± 1.2 years at the beginning of the study, underwent cerebral MRI with a 0.5 Tesla GE MR Max system. Morphological analyses were performed on coronal slices, 5 mm thick, obtained with a T1-weighted spin echo sequence (TR 600 ms; TE 25 ms). Image analysis was performed with a RAS 2000 computerized image analysis system (Amersham Int.). We analyzed volumes of prefrontal lobes (PFL), temporal lobes (TL) and lateral ventricles. White and gray matter were considered together. Analyses were performed for ratios of regional volumes to total cranial volume. All patients were receiving antipsychotic treatment (5.2 ± 3.7 mg/day of halopreridol equivalents). Outcome was evaluated after 24 months from the beginning of the study using the Strauss-Carpenter Outcome Scale. Patients were then divided, considering the median score value, in two groups (good and poor outcome) for each item of the scale.We performed three separate multivariate analyses of covariance (MANCOVA), where variables in analysis were frontal lobe, temporal lobe and lateral ventricular volumes; the between-subjects variation factor was good or poor outcome in each of the Strauss-Carpenter item scores; the covariation factor was the baseline evaluation of the same scores; finally, side (right vs. left) was the within-subjects factor.No significant effects emerged for lateral ventricular and temporal lobe volumes. As for prefrontal lobe volume, analyses pointed out that patients with different outcomes in the areas: severity of symptoms and total Strauss-Carpenter score has different PFL volumes (respectively F = 5.16, df = 1,12, p = 0.04 and F = 6.2, df = 1,12.p = 0.036). As expected, patients showing worse outcome had significantly smaller PFL volumes .Our results indicate a predictive validity of cerebral morphology on symptomatological course and outcome of schizophrenia in neuroleptic treatment. Even if an earlier meta-analysis (Friedman et al., 1992) on the relationship of structural brain imaging parameters to antipsychotic treatment response did not demonstrate a full statistical significance for the whole sample of studies considered, several studies and some of the more recent ones reported data in line with our results. Moreover, our present findings are consistent with earlier reports by our research group indicating neuropathology as a predictor of clinical outcome of both acute, schizophreniform disorder and chronic schizophrenia.