The immunomodulatory effect of the macrolide antibiotic, roxithromycin (RXM) on Langerhans cells (LC) was studied in mice. RXM inhibited the ability of LC to present superantigen and hapten to T cells at 100 microM. The superantigen-presenting activity of LC was more profoundly abrogated by RXM than the hapten-presenting activity. This functional reduction was partly attributed to an RXM-induced decrease in promotion of the expression of major histocompatibility complex class II molecules on LC. On the other hand, RXM down-modulated the production of interleukin-1 beta by LC at a lower concentration of 10 microM than concentrations that inhibited antigen presentation. These results imply that RXM exerts therapeutic effectiveness via not only bacteriocidal action but also inhibitory effect on the LC ability in T-cell-mediated cutaneous diseases that can be exacerbated by skin-colonized Staphylococcus aureus.