To assess the immunogenicity of adalimumab, a human anti-TNF-alpha mAb, we evaluated the formation of antibodies to adalimumab, efficacy and adverse events among 15 patients with highly active rheumatoid arthritis. Four patients were treated with adalimumab as monotherapy, and 11 patients with concomitant DMARDs. Disease activity was measured by DAS28. The antibodies were detected by ELISA. Thirteen (87%) patients withdrew from therapy within 45 weeks and overall 13 (87%) patients showed antibodies to adalimumab including 11 patients who withdrew from therapy. In four patients without concomitant DMARDs and in nine patients with concomitant DMARDs, we detected anti-adalimumab antibodies. Overall, five of seven patients with adverse drug reactions and all nine patients with lack of efficacy were associated with the formation of antibodies. Two antibody-positive patients developed an exantheme. The results indicate that adalimumab is, in spite of its fully human sequences, immunogenic and induces antibodies in a high rate of adalimumab-treated patients.