As a test of the significance of previously described biochemical abnormalities in thiamine-dependent enzymes in brains and other tissues in patients with Alzheimer's disease, a double-blind, placebo-controlled, crossover, outpatient pilot study compared the effects of 3 g/d of oral thiamine hydrochloride for three months with those of a niacinamide placebo. Eleven moderately impaired patients with "probable Alzheimer's disease" by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria completed the study. All patients were well nourished and had no stigmata of dietary thiamine deficiency. Their initial mean +/- SEM Mini-Mental State Examination score was 14.2 +/- 1.4, and the mean age was 72 years. Global cognitive rating by the Mini-Mental State Examination was higher during three months with 3 g/d of oral thiamine hydrochloride than with niacinamide placebo. Behavioral ratings, however, did not differ significantly, nor did clinical state when it was judged subjectively.