Three methods of determination of anti-DNA antibodies were compared. The indirect immunofluorescence method after exposure to animal DNA (IF) and Farr's radio-immunological method with bacterial DNA labelled with C14, gave highly similar results, although there were some cases in which Farr's method gave a negative and the IF method a positive result. In part, this discordance appears to be accounted for by the variable affinity of the anti-DNA antibodies for DNA. The counter-immuno-electrophoresis method (CIEP) on the other hand, gave very different results: positive reactions in a large proportion of normal sera and a considerable proportion of false-positive and false-negative results in disseminated lupus erythematosus. It is concluded that until the CIEP method is made more reliable by technical refinement, determination of anti-DNA antibodies may be carried out by either the IF or the radio-immunological method, but a double-check, by application of the two methods at the same time, is highly advisable.