U46619, a thromboxane A 2 mimetic, caused tyrosine phosphorylation of several proteins in rabbit platelets. Among them, 42 kDa protein was identified as a mitogen-activated protein kinase (MAPK). U46619 activated MAPK in a concentration-dependent manner, measured by incorporation of 3 2 P to a specific substrate for MAPK. U46619 also liberated [ 3 H]arachidonic acid in a concentration-dependent manner. The U46619-induced MAPK activation and [ 3 H]arachidonic acid liberation were inhibited by SQ29548 and by the removal of external Ca 2 + ions. This is a first demonstration that TXA 2 activates MAPK accompanied with arachidonic acid liberation in rabbit platelets.