C6 glioma cells possess both β1- and β2-adrenergic receptors. In response to exposure to isoproterenol, these cells down-regulated the mRNA for both β1- and β2-adrenergic receptors in a manner that indicates an independent regulatory mechanism for each subtype. In particular, the mRNA species for the β1-adrenergic receptor initially increased two-fold during the first hour of exposure before decreasing to 40% of initial levels at 4 hours after exposure. In contrast, the β2 mRNA species decreased rapidly and monotonically to 20% of initial levels by 2 hours. The unique response to isoproterenol of each subtype was blocked by the appropriate subtype-specific antagonists, betaxolol and ICI 118,551. In addition, β-adrenergic receptor mRNA down-regulation was observed in association with contact inhibition, suggesting that events other than receptor occupancy can regulate β-adrenergic receptor mRNA levels. © 1990.