Stearoyl-CoA desaturase (SCD) is a regulatory enzyme in lipogenesis, catalyzing the rate-limiting step in the overall de novo synthesis of monousaturated FA, mainly oleate and palmitoleate from stearoyl- and palmitoyl-CoA, respectively. Oleate and palmitoleate are the major monounsaturated FA of membrane phospholipids, TG, wax esters, cholesterol esters, and alkyldiacylglycerol. Several SCD gene isoforms (SCD1, SCD2, SCD3, and SCD4) exist in mice, and two have been characterized in humans. SCD1 gene expression in liver cells is regulated by numerous stimuli including diet and hormones. We are interested in why SCD is such a highly regulated enzyme even though oleate, the major product of this enzyme, is one of the most abundant FA in the diet and is therefore readily available. Dietary oleate is also well known for its TG-lowering effects and, as a major component of olive oil, is expected to have beneficial effects. However, high SCD activity has been implicated in diabetes, obesity, atherosclerosis, and cancer in several animal models; therefore, the role that de novo oleate plays in these disease states has to be carefully evaluated. By using SCD1-/-mice, which are deficient in tissue oleate, we begin to learn more about the physiological role of SCD gene expression and oleate in normal and disease states.