The efficacy of tacrine for treatment of Alzheimer's has been demonstrated in several clinical trials but has not been assessed in cases complicated by medical and psychiatric comorbidities. Additionally, the benefit-risk ratio of tacrine is small, so it is best administered with carefully developed guidelines that specify this ratio for patients and families. On the basis of guidelines developed for the Johns Hopkins Dementia Research Clinic, tacrine treatment was offered to 162 patients with probable Alzheimer's. Only 35 accepted, and only 22 continued on tacrine beyond 3 months. The latter group declined by 1.36 points over 1 year on the Mini-Mental State Examination, significantly less than expected. The authors conclude that, if used in the context of clinical guidelines, tacrine is an effective treatment for Alzheimer's.