Impaired responsiveness of platelets to epinephrine (epi) and other catecholamines (CA) has been reported in approximately 20% of the healthy Korean and Japanese populations. In the present study, platelet aggregation induced by epi was potentiated by RO 31-8220 (RO) or G$ddot{o}$ 6983 (G$ddot{o}$). Phosphorylated Akt (p-Akt) was very low in epi-stimulated PRP from CA-hypo- responders (CA-HY), whereas it was detected in those from CA-good responders (CA-GR). RO and G$ddot{o}$ increased p-Akt, one of the major downstream effectors of phosphoinositol-3 kinase (PI3K), in epi-stimulated PRP from both groups. Wortmannin, a PI3K inhibitor, attenuated the RO or G$ddot{o}$-induced potentiation of p-Akt in epi-stimulated PRP, suggesting positive effects for RO and G$ddot{o}$ on PI3K. $TXA_2$ formation was increased by the addition of either RO or G$ddot{o}$ in epi-stimulated platelets. The present data also suggest that impaired Akt phosphorylation may be responsible for epinephrine hypo-responsiveness of platelets.