Although there is evidence that some schizophrenia patients may have altered regional cerebral blood flow patterns, few studies have addressed the relationship between cortical activity and changes in psychiatric symptoms following treatment, particularly in the elderly. We took advantage of an existing safety and tolerance study of risperidone in the elderly and examined the possible relationship between changes in psychiatric symptoms following risperidone and changes in relative cortical perfusion in a group of 6 elderly schizophrenia patients. All subjects were at least 65 years old and diagnosed with schizophrenia according to DSM-III-R criteria. The patients were assessed using the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) and Mini-Mental Status Examination (MMSE) and had single photon emission computed tomography (SPECT) studies before and at least 3 weeks after change of their previous neuroleptic to risperidone. The frontal/total cortex and temporal/total cortex counts in the slice ratios, and 99mTechnitium-hexamethylpropylene amine oxime (99mTc-HMPAO) percentage uptake in the whole cortical area in the slice were used for data analysis. With risperidone, patients (age 66-81) scored better on the PANSS, particularly in the positive symptom subtests. The changes in positive symptom scores correlated directly with those in frontal and temporal relative activity and 99mTc-HMPAO percentage uptake in the whole cortical area in the slice. Our findings suggest that the improvement in psychotic symptoms after risperidone is associated with a decrease in frontal and temporal activity and a reduction in 99mTc-HMPAO percentage uptake in the entire cortical area in the slice and agree with data from younger populations. Comparative studies assessing the therapeutic impact of neuroleptics on cortical activity in different age groups could be helpful in examining both the mechanisms of action of various drugs and the links between symptoms and specific brain areas.