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Histones are lysine-rich and arginine-rich basic proteins of eukaryotic cells which are predominantly found as complexes with DNA. Antibodies to histones are detected in approximately 30% to 60% of patients with systemic lupus erythematosus (SLE), but their presence in about 95% of patients with drug-induced lupus is more important diagnostically. Drug-induced lupus (primarily caused by procainamide and hydralazine) is clinically similar to SLE, except that the former patients do not have kidney or central nervous system involvement and they do not demonstrate the multiple types of antinuclear antibodies (ANAs) often found in SLE patients. In addition, drug-induced antihistone antibodies react strongly with H2a/H2b fragments (in procainamide-induced SLE) as well as H3 and H4 (in hydralazine-induced SLE). In patients with drug-induced lupus, antihistone antibodies are usually the only ANAs, although antibodies to denaturated DNA have been detected in a small percentage of patients. Antihistone antibodies also occur in approximately 20% of patients with rheumatoid arthritis.