The actions of indomethacin on the effects produced by ethanol were determined in rats and mice by measuring motor coordination (Rotorod test), sleep times, and body temperatures. Mice receiving indomethacin in combination with ethanol slept shorter times than those receiving ethanol alone. The blood and brain ethanol concentrations at time of awakening were significantly higher in the mice receiving the combination of drugs. Ethanol actions on motor impairment in rats and mice and on hypothermia in mice were not altered by pharmacologically relevant doses of indomethacin. The data show that indomethacin antagonizes only some of the observed effects of ethanol. It is suggested that a common mechanism, such as prostaglandin synthesis, is not involved in the interactions of both drugs.