Five hundred and eighty dogs with at least one clinical sign compatible with a systemic lupus erythematosus (SLE) were entered in a prospective study aimed at evaluating the prevalence of antinuclear antibodies (ANAb). SLE was diagnosed in 38 of these dogs (group A) which fulfilled at least four American Rheumatism Association (ARA) criteria; of these, sixteen had ANAb titers greater than or equal to 4096. The 23 dogs which met three or two ARA criteria (group B) had an ANAb geometric mean titer (GMT) of 259. Dogs (group C) with only 1 criterium had an ANAb GMT of 75. Anti-ds-DNA Ab were present in 6 dogs from group A (16%), and 2 dogs from group B (9%). Anti-histone Ab were present among dogs from group A, B and C with frequencies of 81%, 67% and 26%, respectively. Among dogs from group A, the ANAb titers and the levels of anti-histone Ab correlated positively when individual sera were considered. Antibodies against the soluble nuclear antigen (SNA) were detected in 74%, 39% and 13% of the dogs from groups A, B and C, respectively. Antibodies initially described in human SLE also exist in SLE dogs. Anti-Sm Ab were found in 24% of dogs in group A. With anti-RNP Ab the frequency was still lower (10%). However, two other types of anti-SNA Ab against RNAse and trypsin-resistant antigens, not found in human "reference sera", were often detected. The first type (anti-type 1 Ab) was found in 26% and 9% of group A and group B, The first type (anti-type 1 Ab) was found in 26% and 9% of group A and group B, respectively; the second type (anti-type 2 Ab) is less frequent, and was found in 13% and 17% of group A and B, respectively. It appears that testing for anti-Sm, anti-type 1 and anti-histone Ab should be performed in order to improve the diagnosis of SLE in dogs.