Objective: This study examined whether men and women with schizophrenia and other psychotic disorders differ in brain activation as measured via SPECT scans. Method: Participants included 217 males and 87 females with a mean age of 32.25 years (SD = 11.97). The sample was predominantly Caucasian (62.2%). Participants were given a SPECT scan at baseline level and while concentrating on the Conners' Continuous Performance Test, from which cerebral blood flow (CBF) measures were derived. Results: A MANOVA was conducted at the .05 level and revealed significant differences between males and females on CBF at baseline, Wilks' λ= .582; F(17, 286) = 12.066, p = .000. Women demonstrated significantly greater CBF than men in bilateral limbic areas, basal ganglia, cerebellum, frontal lobe, parietal lobe, motor sensory cortices, left temporal lobe, and the vermis. Female participants did not yield significantly greater CBF in bilateral occipital areas nor the right temporal lobe. Significant differences were also found during concentration, Wilks' λ= .586; F(17, 276) = 11.487, p = .000. Women showed the same baseline pattern of CBF, with the addition of the right frontal and right parietal lobes not yielding significant differences. Conclusion: Analyses indicated significantly higher perfusion across the majority of brain regions in women as compared to men. These findings suggest that at rest, women with schizophrenia and other psychotic disorders have more active brains than men. A change in CBF exists during concentration, with women showing fewer differences in activation. This may be related to the prevalence of positive symptoms in women and negative symptoms in men. SPECT scans may be useful in localizing brain activity in this population. Future research should attempt to determine which areas are activated the most in women.