The effect of AY-25,712 [2-methyl-2-phenyl-3(2H)-furanone-5-carboxylic acid] on various aspects of free fatty acid (FFA) and triglyceride metabolism was studied in male rats. Serum triglycerides were lowered by a single oral dose of AY-25,712 or nicotinic acid, but not of clofibrate. Unlike with clofibrate, when AY-25,712 or nicotinic acid was given in the diet, serum triglycerides were not affected. In vitro, both AY-25,712 and nicotinic acid suppressed the theophylline-induced FFA release by epididymal fat pads, but had no effect on lipolysis induced by norepinephrine. Both AY-25,712 and nicotinic acid enhanced the activity of adipose tissue lipoprotein lipase. The initial decrease in plasma FFA and triglycerides, and in liver triglycerides after a single oral dose of nicotinic acid was followed by a rebound to levels which, at later time intervals, wee significantly higher than in controls. AY-25,712 was more potent than nicotinic acid in lowering plasma FFA and triglycerides as well as liver triglycerides, but produced no such rebound effect. The data show that, except for the absence of this rebound effect, the mode of action of AY-25,712 in rats resembles that of nicotinic acid and differs from that of clofibrate.