The relationship between hypocholesterolemia and anemia has been recognized in humans. However, no metabolic studies in humans have been reported, nor has an animal model been developed to investigate the effects of anemia on cholesterol metabolism. We have identified an animal model, the 'sex-linked anemic' (gene symbol, sla) mouse, characterized by iron deficiency anemia, to study the relationship between anemia and cholesterol metabolism. Results from our studies showed that the serum cholesterol was significantly lower in anemic male SLA mice compared to non-anemic littermates. The lower serum cholesterol observed in anemic SLA mice was related to a decreased in vivo hepatic cholesterol synthesis. However, the decreased hepatic cholesterol synthesis in anemic SLA mice was not due to a block at the primary regulatory site, the hydroxymethylglutaryl-CoA reductase, nor at one of the secondary regulatory sites: the acetoacetyl-CoA thiolase and hydroxymethylglutaryl-CoA synthase.