The impact of a low-fat diet and a high-MUFA diet on apolipoprotein A-I (apoA-I), apoA-II, and VLDL-apoB-100 metabolism in conditions of unrestricted (ad libitum) energy intake was compared in 65 men randomly assigned to one of two predefined experimental diets. A subsample of 18 men participated in the kinetic study. Before and after the 6–7 week dietary intervention, kinetic subjects received a primed-constant infusion of [5,5,5-2H3]l-leucine for 12 h under feeding conditions. ApoA-I production rate (PR; −31.5%; P < 0.001) and fractional catabolic rate (FCR; −24.3%; P < 0.05) were significantly decreased after the low-fat diet. These changes in apoA-I PR and FCR with the low-fat diet were also significantly different from those observed with the high-MUFA diet (P < 0.01 and P < 0.05, respectively). ApoA-II FCR was significantly increased in the high-MUFA group only. No significant within- or between-diet difference was found in VLDL-apoB-100 PR or FCR.These results emphasize the differential impact of the low-fat diet and high-MUFA diet on HDL metabolism.