The immunoglobulin class and subclass distribution of antibodies to double-stranded (ds) DNA has been determined in NZB/W F1 hybrid mice by a double antibody radioimmunoassay. The results show that there are marked age- and sex-related variations in the class and subclass distribution of these antibodies. In young mice of both sexes, the predominant anti-ds DNA antibody was of the IgM class, but as the animals aged, there was an increase in the level of the IgG2a and IgG2b antibodies. An apparent switch from predominantly IgM to IgG antibody occurred in females before males and at about the age of onset of overt immune complex disease in these animals. The possible significance of these results in the pathogenesis of the murine lupus syndrome is discussed.