Conjugated linoleic acid (CLA) has been shown to reduce body fat and increase lean body mass in mice, rats, and pigs. A recent human trial indicated that CLA may work more effectively if used for prevention of body fat deposition and weight gain. To test this hypothesis, we conducted 2 experiments using relatively old mice (older than 6 mo): experiment 1, supplementation of CLA during dietary restriction and experiment 2, supplementation during ad libitum feeding followed by restriction. In experiment 1, there were significant effects of diet restriction and CLA supplementation on body composition, while CLA decreased body fat content in ad libitum diet but not significantly during diet restriction. In experiment 2, CLA fed animals had body weights similar to restricted animals and CLA significantly reduced body fat (significantly lower than prior to and post restriction, or pair fed). This suggests that CLA exerted modulation of body fat independent of reduced food intake. Based on these results, we concluded that CLA may be more effective at protecting against fat mass regain following weight loss than as a weight loss treatment.