Both hydrophilic and hydrophobic azo radical initiators are useful for in vitro studies on lipid peroxidation and its inhibition by antioxidants. In the present study, a new lipophilic azo compound, 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile) (MeO-AMVN), was introduced and its action as an initiator of lipid peroxidation was examined. MeO-AMVN decomposed about 15 times as fast as 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN), a widely used lipophilic azo initiator, and MeO-AMVN-initiated free radical-mediated peroxidations of lipids in organic solution and in micelles, membranes, and low-density lipoprotein in aqueous dispersions with much smaller concentration than AMVN. The rate of chain initiation by MeO-AMVN varied significantly with the medium and decreased with increasing viscosity of the medium. The advantage and cautions for using MeO-AMVN as a lipophilic radical source have been discussed and it has been concluded that MeO-AMVN, when properly used, is a useful radical initiator of lipid peroxidations especially in micelles, membranes, and lipoproteins.