Methylphenidate, pemoline, and protriptyline were studied for their treatment efficacy in narcolepsy. A low, intermediate, and high dose level of each drug was studied for 1 week. For methylphenidate the doses were 10, 30, or 60 mg/day; for pemoline, 18.75, 56.25, or 112.5 mg/day; and for protriptyline 10, 30, or 60 mg/day. The order of dose levels was random from subject to subject and the daily dose was divided into thirds and taken in identically appearing capsules morning, noon, and afternoon. Subjects were 6 narcoleptic patients studied on methylphenidate (5 women and 1 man; mean age 54.5 + 11.7 years), 7 narcoleptic patients studied on pemoline (5 women and 2 men; mean age 43.0 + 7.1 years), and 4 narcoleptic patients studied on protriptyline (2 women and 2 men; mean age 42.5 + 16.9 years). Testing consisted of day-long sessions occurring at the end of each dose level and involving a clinical status questionnaire as well as maintenance of wakefulness, Wilkinson addition, and Digit-Symbol Substitution tests. Results were compared with 9 control subjects with no sleep disorder (5 women and 4 men; mean age 39.2 + 8.4 years) who were given placebo that was purported to be a "stimulant drug" and tested in a similar manner. Results demonstrated profound differences in ability to stay awake and perform between narcoleptic patients and controls. Data also suggested that methylphenidate significantly improves ability to stay awake. Pemoline seems to improve ability to perform. Protriptyline does not significantly alter ability to stay awake or to perform.