For nearly a decade, the fundamental questions of my laboratory have been, "Is endothelin an alternate activating pathway for leukocytes in injury, ischemia, and sepsis?" and "Is monocyte/macrophage-produced endothelin a clinically relevant factor in the vasoconstriction observed in some vascular beds with injury and infection?" Because the motto of my lab is "If we knew what we were doing, we wouldn't call it research," I must confess that after 10 years of investigating and thinking about these questions, I still do not know the answer to either of them.