A 36-year-old male presented with bilateral, anterior, chronic uveitis, with cystoid macular edema. Decimal visual acuity was 0.25 in the right eye and 0.20 in the left eye. Ankylosing spondylitis had been diagnosed 13 years previously, with peripheral and axial involvement. He had no history of extra-articular manifestations of ankylosing spondylitis before this uveitis attack. Treatment with the anti-tumor necrosis factor agent etanercept was initiated 5 months before the attack of uveitis. Slit-lamp biomicroscopy, laser-flare photometry, optical coherence tomography, chest radiography, angiotensin-converting-enzyme test, mycobacterial culture from gastric lavage, serology tests for syphilis, brucellosis, toxoplasmosis, toxocarosis, antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, antimyeloperoxydase antibodies and antiproteinase 3 antibodies. Atypically severe HLA-B27-positive uveitis, in a patient with ankylosing spondylitis treated with etanercept. Intensive topical corticosteroid and cycloplegic treatment, subtenon triamcinolone acetonide injection, switch in treatment from etanercept to infliximab followed by discontinuation of tumor necrosis factor inhibitors, intravenous pulses of methylprednisolone followed by oral corticosteroids, and intravenous cyclophosphamide.