Allergic diseases are hypersensitivity disorders associated with the production of specific immunoglobulin E (IgE) to environmental allergens. Interleukin (IL)-4, produced primarily by CD4(+) T cells, is an important stimulus for the switch of the antibody isotype to IgE in both mice and humans. In this study we investigated the inhibitory activity of IL-4 production in activated T cells by screening ceramide derivatives prepared by solid phase combinatorial chemistry. Many ceramide derivatives significantly inhibited IL-4 production in T cells. In particular, ceramide derivatives with a lauroyl group showed strong inhibitory activities on IL-4 production in both phorbol 12-myristate 13-acetate (PMA)-activated EL4 T cells and antigen-primed cells, suggesting that they can be used as compounds for the development of anti-allergic agents.