The immunochemical specificity of the immunofluorescent Crithidia luciliae method for detection of antibodies to double-stranded DNA (dsDNA) was confirmed by demonstrating abolition of staining by DNase digestion and by absorption with dsDNA. This method was less sensitive than a Millipore filter method for detecting antibodies to DNA. It was positive only in subjects with systemic lupus erythematosus or drug-induced antinuclear factors. This technique appears suitable for study of the immunochemical characteristics fo antibodies to dsDNA.