A biallelic polymorphism (--174 G/C) within the interleukin-6 (IL-6) promoter reportedly has functional importance through the modulation of IL-6 expression in vitro and in vivo. We performed a population-based case-control study to analyse the association of the --174 G/C polymorphism with disease susceptibility and clinical manifestations in 211 German patients with systemic lupus erythematosus (SLE). There were no significant differences in allelic and genotypic frequencies between patients and healthy controls. Comparing patients with various disease manifestations, we found an association of the --174 G allele with discoid skin lesions (Pc=0.034) and anti-histone antibodies (Pc=0.009). The IL-6 promoter polymorphism --174 G/C does not contribute significantly to disease susceptibility, but predisposes to distinct clinical and immunological features. A genetically determined high IL-6 response may have a pathogenic role under these conditions.