Addition of endothelin-1 to cultured rat brain capillary endothelial cells induced a 2.7-fold activation of phospholipase A2, as evidenced from the release of [3H]arachidonic acid from prelabelled cells. Half maximum activation by endothelin-1 was observed at 1 nM. The action of endothelin-1 was not mimicked by low concentrations of endothelin-3 and it was largely suppressed by BQ-123, suggesting the involvement of an ETA receptor subtype. It is suggested that the activation of phospholipase A2 by endothelins plays a role in the development of delayed cerebral vasospasm following subarachnoid hemorrhage.