An enzyme-linked immunosorbent assay done with microtiter plates and capable of testing hundreds of sera per day has been developed and evaluated for the detection of antibodies to DNA. An increase of antibody levels with age in New Zealand White mice was demonstrated. We demonstrated for the first time that New Zealand White mice infected with Schistosoma mansoni for 10 weeks have higher anti-DNA antibody levels than controls. We demonstrated that NIH outbred albino mice infected with S. mansoni for 18 weeks developed anti-DNA antibodies by 6 weeks of infection, and found a suggestion that immune complexes are present in the circulation by 9 and 11 weeks of infection. A reasonable correlation between visual end-point titration readings and spectrophotometric readings was found. However, spectrophotometric measurements revealed more subtle changes in antibody concentrations that did visual readings. These results demonstrate the usefulness of the micro-ELISA technique for the detection of anti-DNA antibodies in experimental animals, and warrant further evaluation of this test with the serum of humans with autoimmune diseases such as systemic lupus erythematosus.