Alacepril, a sulfhydryl-containing angiotensin-converting enzyme inhibitor has been suggested to have antioxidant or free radical scavenging effects. Recently, small, dense low-density lipoprotein (LDL) has been reported to be particularly atherogenic due to its high susceptibility to oxidative modification. The effects of the oral administration of alacepril (50mg/day) on LDL particle size were examined in 12 patients with essential hypertension. The relative migratory distance (RMD) of the predominant densitometric peak of LDL from that of very low-density lipoprotein to that of high-density lipoprotein in a 3% polyacrylamide gel electrophoreis was determined as a measure of LDL particle size. RMD was shown to be inversely correlated with LDL particle diameter and RMD above 0.36 corresponded to a LDL particle diameter <25.5nm or small, dense LDL according to the preliminary experiment. Alacepril (50mg/day) was administered for 3 months. No significant alteration was observed in RMD values after administration of alacepril to the patients. However, RMD decreased in the 6 patients with small, dense LDL, suggesting that their LDL particle size had increased, and serum α-tocopherol levels increased in 5 of the 6 patients. In conclusion, the oral administration of 50mg of alacepril for 3 months enlarged LDL particle size and increased serum vitamin E levels in patients with small, dense LDL, suggesting its favorable effects on lipid metabolism by antioxidative reaction. Alacepril may be useful, especially in the treatment of hypertensive patients combined with dyslipidemia with small, dense LDL.