The hypothesis was investigated that the nitric oxide (NO) synthase intermediate, N%hydroxy-L-arginine (HOArg), is an arginase inhibitor in rabbit or rat alveolar macrophages. Exogenously applied HOArg strongly inhibited the arginase activity present in these cells (ICs0 > 15 ItM), and attenuated L-[3Hlarginine transport (ICs0 -> 500 ~M) in rabbit alveolar macrophages. Moreover, up to 37 ~M HOArg were detected in the conditioned medium, but not in the lysate, of rat alveolar macrophages exposed to bacterial lipopolysaccharide for 18 h. HOArg may thus be a potent endogenous arginase inhibitor in these cells which increases the availability of L-arginine for NO biosynthesis.