Anti-TNF-alpha therapies are promising new strategies in the treatment of rheumatoid arthritis (RA). Despite good clinical efficacy and tolerance, the possible occurrence of drug-induced autoimmune disorders remains a matter of concern. Induction of antinuclear (ANA) and anti-DNA antibodies is observed in some patients treated with TNF-alpha inhibitors (anti- TNF-alpha antibodies) or soluble TNF-alpha receptor. Of concern is the possibility of induction of true lupus erythematosus by TNF blockers. Few cases without major organ involvement were reported to be associated with infliximab treatment that resolved after anti-TNF discontinuation. Only four cases have been described with the use of etanercept. We report a new case of infliximab-induced lupus syndrome and two new cases of etanercept-induced lupus syndrome in three patients with RA, all of whom had previous isolated positive ANA.