Sera of patients with symptoms of connective tissue diseases were investigated for the presence of antinuclear antibodies by indirect immunofluorescence on rat liver substrate. In positive cases antibodies to native DNA were determined by radioimmunoassay and by counterimmunoelectrophoresis. Twenty seven selected sera were also tested by indirect immunofluorescence on Crithidia luciliae substrate to test the sensitivity and specificity of this method. Immunofluorescent antinuclear antibodies could be found in all groups of connective tissue diseases while anti-native DNA antibody was demonstrated in higher amount only in the cases of systemic lupus erythematosus and therefore determination of anti-native DNA antibody may be helpful in the diagnosis of oligosymptomatic SLE. Counterimmunoelectrophoresis and immunofluorescence on Crithidia smears may serve as screening methods for anti-native DNA while radioimmunoassay provides a quantitative determination, although there are minor differences in the sensitivity and the specificity of these three methods.