A number of simple coumarins with different patterns of substitution were tested on activated polymorphonuclear leukocyte superoxide generation and superoxide scavenging using the reduction of nitroblue tetrazolium. The most effective compound was fraxetin, which showed a better potency as an inhibitor of superoxide radical generation than as a scavenger. From the structure-activity study it can be deduced the importance of an ortho-dihydroxyl function, especially at the position 7, 8. Blockade of active hydroxyl groups by methylation or glycosylation decreases the activity. None of the coumarins were cytotoxic on leukocytes as assessed by lactic dehydrogenase activity release. Inhibition of superoxide generation in activated neutrophils may play a role in the vasoprotective effects of simple coumarins.