Recent reports have suggested that erythromycin (EM) might have immunomodulatory activities. Roxithromycin (Rox) is a new macrolide, which has more favorable pharmacokinetic properties than EM. The current studies therefore examined the effects of Rox on the in vitro function of human T cells. Interferon-γ (IFN-γ) production was induced from highly purified T cells and CD45RA (-) T cell subsets from normal individuals by stimulation with immobilized anti-CD3. Rox at its pharmacologically attainable concentrations suppressed the IFN-γ production of CD45RA (-) T cells stimulated with immobilized anti-CD3, but not that of unfractionated T cells. EM also preferentially suppressed the IFN-γ production of CD45RA (-) T cells, but less effectively than Rox. Rox also preferentially suppressed the IL-2 production of immobilized anti-CD3 stimulated CD45RA (-) T cells. These results suggest that Rox may preferentially suppress the IFN-7 production of memory T cells, but not that of naive T cells. Moreover, the data call for considering Rox as a possible immunomodulator for the treatment of various autoimmune disorders in which the abnormal function of CD45RA (-) T cells is involved, especially Behcet's disease.