There is evidence in both murine and human lupus that the production of anti-DNA antibodies may be triggered by environmental antigens. To explore this further, we studied the serum of 10 nonautoimmune individuals immunized with a polyvalent pneumococcal polysaccharide vaccine. All 10 patients showed a rise in the titer of antipneumococcal antibodies bearing an anti-DNA-associated idiotype. The antipneumococcal response was specific as no idiotypic antitetanus antibodies were detected. Furthermore, no anti-DNA antibodies were present in postvaccination sera. The molecular analysis of antipneumococcal and anti-DNA antibodies bearing a common idiotype will help elucidate how foreign antigen might lead to the production of anti-DNA antibodies in susceptible individuals.