METHODS Seventeen patients with subacute cutaneous lupus erythematosus (SCLE) were compared with 15 patients with discoid lupus erythematosus (DLE) to evaluate the relationship of 60- and 52-kd Ro/SSA autoantibodies to the clinical diagnosis and to evaluate assays for anti-Ro/SSA. RESULTS All serum samples from patients with SCLE had precipitating anti-Ro/SSA antibodies in immunodiffusion, and all had high titer anti-60-kd Ro/SSA in enzyme-linked immunosorbent assay. Immunoblotting was inadequately sensitive for detecting anti-60-kd Ro/SSA. Fifteen patients with SCLE had anti-52-kd Ro/SSA (11 high titer, four low titer). Only one of the 15 patients with DLE had precipitating, high-titer anti-Ro/SSA. Nine other patients with DLE had low-titer anti-60-kd Ro/SSA, and four had low-titer anti-52-kd Ro-SSA. Low-titer anti-Ro/SSA did not confer an increased risk for photosensitivity in the DLE group. CONCLUSIONS High-titer, precipitating antibodies to Ro/SSA are typical of SCLE and unusual in DLE. Low-titer, nonprecipitating antibodies to Ro/SSA are common in DLE and could be an indication of pathogenic factors shared with SCLE. However, low titers of anti-Ro/SSA do not confer a significant risk for SCLE skin lesions. For the purpose of clinical evaluation of skin disease, immunodiffusion assays for anti-Ro/SSA are cost-effective and informative.