Peroxynitrite (ONOO-) is a potent oxidant implicated in a number of pathophysiological processes. The activity of ONOO- is related to its accessibility to biological targets before its spontaneous decomposition (t1/2 approximately 1 s at pH 7.4, 37 degrees C). Using model phospholipid vesicular systems and manganese porphyrins as reporter molecules, we demonstrated that ONOO- freely crosses phospholipid membranes. The calculated permeability coefficient for ONOO- is approximately 8.0 x 10(-4) cm.s-1, which compares well with that of water and is approximately 400 times greater than that of superoxide. We suggest that ONOO- is a significant biological effector molecule not only because of its reactivity but also because of its high diffusibility.