Abstract Epinephrine (Epi) infusion influences platelet activation markers in vivo, but in vitro studies have mainly examined supraphysiologica] Epi concentrations and have yielded conflicting results. In this study whole-blood flowcytometric measurements of platelet fibrinogen binding and P-selectin expression were used to compare enhancement of ADP (0.1 to 10 /irnol/L)-induced platelet activation by Epi infusion in vivo (0.1 and 0.4 nmol · kg"1 · min"1) and by Epi in vitro (10 and 50 μmol/L) in nine healthy volunteers. ADP caused concentration-dependent increases in the percentage of platelets that bound fibrinogen (from 4.4 ±0.9% to 69.9±4.2%) and that expressed P-selectin (from 4.5±0.5% to 44.2±3.8%). Fibrinogen and P-selectin binding indices (FgBI and PSBI; calculated from mean fluorescence intensity and percentage of positive cells) also increased from 0.18 ±0.03 to 11.70±1.99 for FgBI and from 0.22±0.03 to 2.34±0.29 for PSBI. Epi concentration-dependently enhanced fibrinogen binding and P-selectin expression in vitro (by ≥30% at the midportion of the ADP curve at 10 nmol/L Epi; (P.001 for both by ANOVAs). High-dose Epi infusion enhanced FgBI similarly and increased maximal P-selectin expression by 38%. Epi (50 nmol/L in vitro) enhanced platelet activation further, whether samples were taken with or without prior Epi infusion. Total expression of gfycoprotein Ilb/IIIa was unaffected by Epi infusion, but glycoprotein Ib expression per platelet was reduced (★<.05). These in vivo and in vitro effects of Epi on platelet responses to agonist stimulation indicate a prothrombotic potential for sympathoadrenal activation in humans. (ArterioscUr Thromb. 1994;14:77-84.