An inverse relationship between the concentration of high density lipoprotein (HDL) cholesterol and the development of coronary heart disease (CHD) is well established. It is unclear from the human studies whether this relationship reflects an ability of HDLs to protect against coronary disease or whether a low HDL in coronary patients is simply an epiphenomenon. Recent studies of transgenic mice, however, indicate that HDLs are directly antiatherogenic. The mechanism of the protection is unknown but may relate both to an involvement of HDLs in plasma cholesterol transport and to a range of non-lipid transport functions of HDLs. It is also unclear from human studies whether specific HDL subpopulations have differing abilities to protect against CHD, although such specificity is suggested from studies of transgenic mice. There is circumstantial evidence that elevating the concentration of HDL cholesterol in human subjects translates into a reduced coronary risk, although it should be stressed that there are still no reports of studies designed specifically to address this issue.