Thirty‐eight patients with mild to moderate Alzheimer's disease (AD) underwent a neuropsychological test battery and 18‐fluoro‐2‐deoxyglucose (FDG) positron emission tomography (PET) before beginning and at the end of a randomized double‐blind study of an experimental treatment. Twelve of the patients took placebo. In the placebo patients, Mini‐Mental State (MMS) score decreased and cortical metabolism increased significantly over the 6‐month course of the study. Correlations of metabolism with neuropsychological performance were stable over time in the placebo group. Cortical metabolism correlated significantly with performance on the Blessed Information Subtest and the MMS and showed trend correlations with performance on the WAIS Digit Symbol and Word Fluency. Patients with high relative occipital metabolism tended to do poorly on word fluency. Low baseline relative metabolism in right frontal cortex and high baseline relative metabolism in left parietal and temporal cortices and in right occipital cortex predicted more 6‐month deterioration on the World Fluency Test, suggesting that frontal metabolic deficits may precede neuropsychological deficits. Correlations of 6‐month change in MMS, Blessed and Digit Symbol performance with initial glucose metabolism were not significant. Copyright © 1995 John Wiley & Sons, Ltd.