We examined the expression and function of β-adrenergic receptor (β-AR) subtypes in both isolated primary rat microglia and a rat microglial cell line. RT-PCR analyses revealed that microglia expressed β1- and β2-ARs but not β3-ARs, whereas rat primary peritoneal macrophages expressed only β2-ARs. Stimulation of β-ARs on microglia by norepinephrine (NE) resulted in an increase in the level of intracellular cAMP and the subsequent expression of interleukin-1β mRNA. These effects were prevented by propranolol. Similar results were obtained with other selective β1-AR agonists and antagonists. β2-ARs on microglia were also functional. It is possible that noradrenergic innervations participate in the control of microglial functions via β1-ARs on microglia in the brain, because NE has high affinity for β1- and β3-ARs but little or no affinity for β2-ARs. It seems physiologically significant that microglia can be controlled by NE, which predominates over epinephrine in the brain, whereas macrophages in peripheral tissues can be controlled by epinephrine, which is at higher levels in peripheral tissues. © 2002 Wiley-Liss, Inc.