Reactive oxygen species (ROS) are implicated in the inflammatory, autoimmune, connective tissue disease, systemic lupus erythematosus (SLE), particularly in respect of processes leading to the formation of pathological anti-DNA antibodies. Exposure to ROS increases the antigenicity of DNA for SLE antibodies, but data on the immunogenicity of ROS-DNA are not conclusive. In this study, we have examined the immunogenicity in rabbits, of DNA modified by three hydroxyl radical generating systems. Additionally, we investigated the antigenicity of UVA, UVB, and UVC irradiated DNA for lupus anti-DNA antibodies. Modification of DNA by both ROS and far UV dramatically increased its immunogenicity; the Fe2+ and H2O2 system resulted in antibodies that recognized both native and modified DNA. In our ELISA system, none of the UV antigens showed any antigenicity above native DNA for SLE sera. The data suggested that different profiles of antigenicity and immunogenicity arise dependent on the method of ROS production, but also that ROS-DNA may be a factor in antigen-driven immune complex formation in SLE.