Immunopathologic cutaneous lesions resembling human systemic lupus erythematosus (SLE) can be induced in mice sensitized to ultraviolet (UV)-irradiated DNA following whole body irradiation with UV light. The lesions are characterized by the formation of immune complexes at different skin sites. The role played by cellular and humoral mediators in the pathogenesis of this experimental model was investigated. The results obtained suggest that inflammation that follows UV radiation is the major factor responsible for this pathology. Accordingly mice that were rendered neutrophil PMN) deficient did not manifest skin lesions, and depletion of C3 complement component left them unchanged. In addition time course studies showed that PMN depletion did not prevent a delayed skin involvement. Thus multiple factors seem to mediate the onset of the immunopathologic changes previously described.