Six patients with dementia of the Alzheimer type (DAT), treated with oral physostigmine and followed from 9 to 27 months (mean +/- SD, 17.8 +/- 7.3 months), were matched for sex, age, initial degree of dementia, and length of follow-up with six control patients who did not receive oral physostigmine. The small sample size precluded drawing definite conclusions about overall efficacy; however, three in the physostigmine group did not deteriorate during the course of follow-up while all of the controls deteriorated although the difference was nonsignificant. The data generated in these patients provides evidence of the safety of long-term trials of oral physostigmine. The possible role of cholinesterase inhibition in retarding the progression of DAT is discussed.