1 The effects of oxygen free radical scavengers and endothelial cell-derived nitric oxide (EDNO) on the death of porcine cultured aortic endothelial cells exposed to exogenous superoxide-[xanthine (0.4 mM)/ xanthine oxidase (0.04 unit ml-')+ diethylenetriaminepentaacetic acid (DTPA, 10 6 The modulatory effects of NO on hydroxyl radical-like activity (=formaldehyde production) from the superoxide generating system was also evaluated in a cell-free superoxide/NO generating system, consisting of xanthine/xanthine oxidase, DTPA, DMSO, and various amounts of a spontaneous NO generator, sodium nitroprusside (SNP) and were compared with those of Fe3". At doses up to 10 gM, SNP concentration-dependently increased the formaldehyde production while the higher concentrations of SNP decreased. The maximum amount of formaldehyde produced by SNP was 5 fold less than that produced by Fe3+ (0.1 mM). Peroxynitrite-induced formaldehyde formation was concentrationdependently inhibited by SNP. 7 We conclude that agonist-stimulated but not basal NO production acts as cytotoxic hydroxyl radical donor as well as the endogenous transition metal when endothelial cells are exposed to exogenous superoxide anion, while the modulatory effect of EDNO is limited by a secondary reaction with hydroxyl radicals.