The effects of 5 different drugs (amphetamine, caffeine, serotonin, sod. salicylate and pentazocine) on the duration of action of two barbiturates (thiopental and pentobarbital) and an intravenous anesthetic (propanidid) were determined in rats. Duration of action was determined by the time elapsing between loss and return of the righting reflexes. All drugs were injected intraperitoneally except propanidid which was administered by the intravenous route. Preliminary experiments indicated that at a dose of 40 mg/kg either of the two barbiturates or propanidid produced loss of the righting reflexes without death. At this dose, however, the duration of action of propanidid was extremely short. However, this dose was selected for subsequent studies. 1. At the dose employed amphetamine shortened the sleeping time of three compounds. 2. Caffeine and theophylline shortened the sleeping time of thiopental and prolonged the duration of action of pentobarbital. 3. Serotonin had no effect on duration of action of the barbiturates but prolonged the sleeping time produced by propanidid. 4. Sod. salicylate significantly prolonged the sleeping time of the barbiturates whereas pentazocine exhibited this effect only in relation to thiopental.