BACKGROUND: Rifabutin-associated uveitis has often been described in patients with HIV. We present the case of a bilateral non-granulomatous uveitis in an HIV negative patient on rifabutin therapy. HISTORY AND SIGNS: A 79-year-old man presented with acute pain and decreased vision in the left eye. He had a 2-months history of Mycobacterium avium pneumonia and was treated with rifabutin, clarithromycin and ethambutol since then. At presentation, the visual acuity was hand movement. On biomicroscopy, the anterior chamber showed inflammatory sings such as hypopyon and early posterior synechiae. Ultrasound revealed no vitreal infiltration. The fellow eye was initially without any pathology. Serological testing and blood cultures were negative. THERAPY AND OUTCOME: The next day, the fellow right eye was also affected showing signs of anterior and posterior uveitis. Following intensive topical steroidal therapy, clinical findings improved within hours. Rifabutin therapy was discontinued. Later on the visual acuity of both eyes improved to 20 / 100. CONCLUSIONS: Bilateral rifabutin-associated uveitis may also occur in an HIV negative patient. A toxic reaction due to concomitant clarithromycin therapy might be causal. Well directed history, intensive topical steroids and the cessation of rifabutin therapy are helpful in the management of such rare uveitis