OBJECTIVE: To investigate whether CD40 and CD40 ligand (CD40L) is expressed in the skin of patients with subacute cutaneous lupus erythematosus (SCLE). METHODS: Six female patients with SCLE were studied. Skin biopsies were obtained from lesional and healthy sunprotected skin. Frozen sections were stained immunohistochemically using monoclonal antibodies to CD4, CD40, and CD40L. As controls we used 5 patients with discoid LE (DLE), 5 with dermatomyositis (DM), 3 with lichen planus (LP), and 2 with erythema multiforme (EM), as well as the normal-appearing skin of 5 healthy volunteers. RESULTS: The CD40 was intensely expressed in all SCLE, DLE, and DM lesions, and only focally in healthy sunprotected skin specimens. The number of CD40+ cells in SCLE dermis was lower than in DLE, similar to that in DM, LP and EM, and higher than in SCLE sunprotected skin. CD40L+ cells infiltrated the SCLE, DLE, DM, LP, and EM lesional dermis, and were more numerous in SCLE lesional skin than in SCLE healthy sunprotected skin. CONCLUSION: We showed that the CD40/CD40L system may represent an important pathway of induction of SCLE lesions. The expression of such costimulatory system in healthy sunprotected skin also may signify that its abnormal activation is constitutive in SCLE, as previously observed in systemic LE.