Aggravation of necrotizing fasciitis (NF) by the administration of non-steroidal antiinflammatory drugs (NSAIDs) has recently been suggested. A rabbit model of streptococcal NF was used to study the effects of parenteral administration of an NSAID on NF evolution and outcome. Of 16 rabbits inoculated with a Streptococcus pyogenes suspension together with staphylococcal alpha toxin, 8 were treated with two doses of 4 mg/kg diclofenac on day 1 after inoculation. Clinical, bacteriological and histological studies were performed until day 10. Under our experimental conditions, NSAID treatment significantly limited NF extension. A specific inverse relationship between the extent of inflammation and bacterial density in NF lesions was observed on day 1 after inoculation in the treated group suggesting that the greater severity of NF in humans treated with an NSAID could be due to the therapeutic delay induced by the misleading clinical effects of the NSAID, and not to inhibition of antibacterial defence.