We examined the relationship between norepinephrine (NE) and hydroxyl free radical (OH) generation on cardiac nerve stimulation. Salicylic acid in Ringer's solution (0.5 nmol microliter-1 min-1) was infused directly through a microdialysis probe to detect the generation of hydroxyl radicals (OH) as reflected by the formation of dihydroxybenzoic acid (DHBA) in the myocardium of anesthetized rats. Sympathetic nerve stimulation increased the release of NE and the formation of DHBA. A positive linear correlation between the release of NE and the formation of 2,3-DHBA (R2 = 0.982) or 2,5-DHBA (R2 = 0.976) was observed. These data indicate that the sustained elevation of NE in the extracellular fluid can be auto-oxidized, which in turn leads (possibly by an indirect mechanism) to the formation of cytotoxic OH free radicals.