Enhanced monocyte activity is present in psoriasis, and benoxaprofen is a drug that inhibits several aspects of monocyte function. To assess a potential pathogenic role of enhanced monocyte function in psoriasis, we determined monocyte chemotaxis and monocyte antibody-dependent cell-mediated cytotoxicity (ADCC) at week 0, 2, 4 and 8 in psoriatics being treated with benoxaprofen. In patients responding to benoxaprofen, normalization of monocyte chemotaxis occurred at week 4, before clinical resolution took place. A significant decrease of monocyte ADCC was also present at week 4, but it was only at week 8, when psoriasis had completely cleared, that monocyte ADCC was completely normalized. In patients receiving placebo or receiving benoxaprofen, but showing no or minimal clinical improvement, monocyte functions remained increased. These results are compatible with the idea that benoxaprofen may improve psoriasis by interfering with monocyte function.