Antibodies directed against neutrophil granulocyte components have gained an increasing importance in diagnosing systemic vasculitis diseases. The present study was aimed to investigate distribution of anti-lactoferrin antibodies in systemic lupus erythematosus, the hydralazine-induced SLE-like syndrome, and in rheumatoid arthritis compared to RA complicated with vasculitis. Antibodies were detected by ELISA and verified by Western blotting and inhibition assay. Sera positive for IgM were absorbed to remove the rheumatoid factor. IgG and IgM anti-lactoferrin antibodies were found in SLE in 5% and 10% respectively. All patients with hydralazine-induced SLE had antibodies of both isotypes and the antibody level declined rapidly after withdrawal of the drug. In rheumatoid arthritis no IgG anti-lactoferrin antibodies were found, but 20% of the patients with vasculitis had IgM antibodies. Anti-lactoferrin antibodies seem partly to discriminate between genuine and hydralazine-induced SLE, which might indicate a pathogenic relevance in drug-induced autoimmunity. In uncomplicated rheumatoid arthritis it can be concluded that anti-lactoferrin antibodies lack clinical, as well as pathogenic relevance.