The scavenger receptor class B type I (SR-BI), a receptor for high-density lipoproteins (HDL), facilitates cholesterol delivery to steroidogenic tissues, and brings excess body cholesterol to liver for excretion. Scavenger receptors are also involved in the internalization of aggregates of Alzheimer's disease (AD) amyloid β-protein, and selective uptake of HDL-associated vitamin E in the brain. Therefore, modulation of the brain SR-BI may affect these processes. The present study examined the expression of SR-BI receptors in murine brain and their regulation by estradiol administration and cholesterol feeding. Liver and brain appeared to express similar SR-BI transcripts. Expression of SR-BI was highest in the adrenals and lowest in the brain. In rats, estradiol administration decreased SR-BI in liver, but increased in adrenals. In mice, estrogen treatment decreased hepatic SR-BI, but interestingly increased the levels of brain SR-BI mRNA. Cholesterol feeding did not alter mouse hepatic SR-BI mRNA, but increased brain SR-BI levels. ATP-binding cassette transporter A1 (ABCA1), involved in cellular cholesterol transport, increased in cholesterol-fed mouse liver, but did not show changes in the brain. These studies suggest that SR-B1 is expressed in the brain and regulated by hormonal and nutritional stimuli, which may influence the pathophysiology of neurological disorders like AD.