Twelve patients who met Research Diagnostic Criteria for Alzheimer's disease (AD) completed a double-blind crossover study comparing oral RS 86, a long-acting and specific muscarinic agonist, with placebo. Cognitive and noncognitive effects were assessed with the Alzheimer's Disease Assessment Scale (ADAS). RS 86 was found to improve ADAS test scores consistently (both cognitive and noncognitive subscales) in seven patients, with a clinically obvious improvement in only two patients. RS 86 produced a significant increase in peak nocturnal cortisol levels, and this increase correlated with improvement on ADAS testing. Similarly, there was a 38% increase in amplitude of the P300 evoked potential with RS 86. The biological findings suggest that RS 86 was effective only to the extent that it enhanced central cholinergic activity.