Vitamin A (retinol) and its analogues (retinoids) are clinically effective in cystic acne and psoriasis, diseases in which neutrophils may constitute major components of inflammatory cell infiltrates. We found that the earliest histopathologic alteration in psoriasis is the disappearance of neutrophils at 2 to 4 weeks after the initiation of therapy with etretinate. Since retinoids may exert anti-inflammatory effects by virtue of an action upon neutrophils, we studied the effects of the following retinoids on discrete neutrophil functions in vitro: retinol, retinyl acetate, retinal, tretinoin, isotretinoin, etretinate, and Ro 10-1670. Although they had no significant effects upon aggregation, chemokinesis, or chemotaxis, all of the retinoids, with the exception of etretinate and Ro 10-1670, profoundly inhibited superoxide anion production and lysosomal enzyme release. Tretinoin and isotretinoin were the most effective inhibitors. We propose that these drugs exert their pharmacologic effects (resolution of inflammatory lesions) by inhibiting the release of mediators of inflammation and by preventing the accumulation of neutrophils in acne lesions when applied topically or systemically, respectively.