Three controlled, double-blind studies of six commonly used preoperative medications were carried out to evaluate their effects on patients' sleepiness, apprehension, restlessness, and confusion, and to determine the incidences of side effects. Separate studies each dealt with two barbiturates, an antihistaminic and a minor tranquilizer, and two narcotic analgesics. In the first study a treatment was pentobarbital, 50 or 150 mg, sodium secobarbital, 50 or 150 mg, or placebo. In the second, a treatment was diazepam, 5, 10, or 15 mg, hydroxyzine, 50, 100, or 150 mg, or placebo. In the third, it was morphine, 5 or 10 mg, meperidine, 50 or 100 mg, or placebo. Each patient received only one treatment; it was randomly assigned and administered intramuscularly 90 minutes before operation. Approximately 30 patients received each treatment. There were 509 subjects in the entire investigation. Subjective responses, scored on a scale of 0 to 9, were obtained 30 and 60 minutes after the injection was administered and were compared with baseline responses obtained before treatment. Independent ratings were also made by a nurse-observer, and an overall evaluation was provided by an anesthesiologist. Interview and medication times were controlled to assure standard measurements throughout all three studies. Five of the six compounds (all but diazepam) increased patients' subjective ratings of sleepiness, and the effects were dose-related. None of the six compounds had any significant effect upon postmedication apprehension as reported by the patients. The only frequently observed side effects, found with all six premedicants, were dry mouth and slurred speech.