It is widely assumed that eicosanoid biosynthesis is initiated by an increase in the intracellular concentration of unesterified arachidonic acid (AA) as a consequence of the activation of cellular phospholipases and/or inhibition of AA reacylation reactions. Here, we describe a mechanism of eicosanoid formation that is entirely dependent on low density lipoprotein (LDL) receptor-mediated delivery of AA to eicosanoid producing target cells. This LDL AA pathway introduces a new regulatory component into the provision of unsaturated fatty acids to mammalian cells.