Although there is evidence suggesting that, in addition to suppressing food consumption, amphetamine reduces body weight by increasing energy expenditure, there is little consistency among the few studies examining that factor. In this experiment, the effect of amphetamine on daily energy consumption, within-day body weights, and hourly measures of metabolic rate (MR) and respiration quotient (RQ) were assessed. Daytime drug injections decreased total energy consumption, produced biphasic changes over time in MR, and persistently lowered RQ values. In contrast, nighttime injections of drug had little effect on energy consumption and MR but did reduce RQ for the first 4 postinjection hours. These effects show that amphetamine effects interact with the circadian organization of behavior and suggest that rodent studies of anorectic agents have more relevance for humans if drugs are given during the night, when rats are normally awake and eating. From this study, it seems clear that amphetamine reduces body weight by altering metabolic rate and fat metabolism in rats when the drug is given during the day.