Intracellular signalling events that govern endothelial responses to shear are incompletely defined. In this study confluent human endothelial cells were subjected to shear. At shear levels of 1.04, 2.92, 5.31 and 8.3 dynes/cm2, which are in the range of those that occur in vessels in venous and arterial circulations, the activity of cPLA2 was increased above control levels. To examine pathways by which cPLA2 may be activated in response to shear, we assayed the p42 isoform of MAP kinase (ERK-2) and found increased activity in cells exposed to shear. Our findings demonstrate for the first time that cPLA2 and MAP kinase p42 are activated by shear in human endothelial cells, and add to evidence from other systems that indicates that the two enzymes have related signalling functions.