Indomethacin, which is considered to be an effective inhibitor of prostaglandin formation, did not affect lipolysis in white fat cells isolated from rats. Exposure of fat cells to indomethacin for periods ranging from 20 to 120 min at either 25 or 37 C did not enhance the subsequent lipolytic response to catecholamines during incubations of from 5 to 120 min. Prior exposure of fat cells to indomethacin also had no effect on the stimulation of cyclic AMP accumulation due to norepinephrine, theophylline, or the combination of both agents. In fat cells previously exposed to norepinephrine, an inhibitor accumulates which interferes with the ability of norepinephrine in the presence of theophylline to stimulate cyclic AMP accumulation. Indomethacin also failed to block the accumulation of this inhibitor. These results indicate that indomethacin (5 to 50 μg/ml) has little, if any, effect on lipolysis and suggest that prostaglandins are not important feedback regulators of adenylate cyclase or lipolysis in isolated white fat cells from rats. (Endocrinology93: 632, 1973)