Three α1‐adrenergic receptor (AR) subtypes have been cloned and characterized, the α1A‐,α1B‐, and α1D‐AR. Evidence suggests functional effects of receptor activation in various tissues is subtype selective. For example, ERK activation in cardiomyoctyes appears to be α1A‐AR dependent, and may be cardioprotective in heart failure. We examined α1‐AR expression and subtype specific ERK activation in human primary arterial smooth muscle cells. Simultaneous co‐expression of all three subtypes was demonstrated by western blot, and further confirmed by RT‐PCR utilizing subtype specific primers. ERK activation was assessed by western blot. Preliminary data suggests ERK activation is blocked by α1D‐AR selective antagonists and is not induced by α1A‐AR selective agonists. If α1A‐AR selective agents were used in heart failure, our data would suggest that ERK activation in peripheral vasculature would be minimal, therefore mitigating concern of α1A‐AR mediated vascular injury as a result of therapy. However, additional subtype selective effects will need to be better defined by future studies.