The pharmacokinetic disposition of intravenous and oral doses of tacrine was determined in 5 elderly patients (aged 64 to 96 y) with the clinical diagnosis of Alzheimer's disease. The bioavailability of the oral formulation was low (9.9% to 36.4%), and the plasma half-life was not altered by route of drug delivery. These data indicate that tacrine elimination occurs by a 1st-order process. Plasma clearance of tacrine varied more than its half-life, which is consistent with a modulating effect of apparent volume of distribution (Vd). Our findings, together with other limited published studies, suggest that use of tacrine for the treatment of Alzheimer's disease (AD) will be confounded by the high interindividual variability in its kinetic disposition.