Function of apolipoprotein (apo) A-IV was studied for its role in cholesteryl ester transfer protein (CETP; lipid transfer protein, LTP) reaction between lipid microemulsions having the diameter of low density lipoprotein, being compared to apoA-I. CETP hardly catalyzed lipid transfer without apolipoproteins. ApoA-IV bound to the surface of the microemulsion in equilibrium with a similar affinity to that of other helical apolipoproteins, and activated the transfer reaction by CETP of cholesteryl ester, triacylglycerol and phosphatidylcholine between the emulsions. The rate of the transfer reaction of cholesteryl ester and triacylglycerol was directly proportional to the amount of the bound apoA-IV to the surface of the emulsion. For phosphatidylcholine, activation was less effective until 40% of total binding capacity of lipid emulsion was occupied by the apolipoprotein. Cholesteryl ester was highly preferred by CETP over triacylglycerol when equal amount of these lipids was present in the core of the apoA-IV-activated emulsion, resulting in almost no triacylglycerol transfer. However, when the emulsion has the core exclusively of triacylglycerol, triacylglycerol was transferred by CETP with the rate in the same order as that of cholesteryl ester transfer. These findings were all comparable to the results with apoA-I, and also consistent with our previous observation for other amphiphilic helical apolipoproteins such as apoA-II, E and C-III.