Summary Tumour necrosis factor (TNF)-alpha antagonists are very effective treatments for immune-mediated inflammatory disorders. Adverse events include severe infections and episodes of lupus-like syndrome, multiple sclerosis-like demyelination and other neuropathies. The pathomechanisms of these autoimmune-like syndromes after TNF-alpha blockade are still unknown. We report a patient with psoriasis who developed a lupus-like syndrome during infliximab treatment, which was finally diagnosed as an exaggerated systemic infection with Borrelia burgdorferi. This case suggests that autoimmune-like syndromes may actually represent pre-existing or newly acquired nonseptic bacterial or viral infections, which have escaped immune surveillance during TNF-alpha blockade. Each autoimmune-like syndrome during TNF-alpha blockade should therefore be carefully examined for potential causative infection.