A Cambodian man and his son concomitantly developed malignant Reiter's syndrome soon after their arrival in France. In both cases generalized skin lesions of pustular psoriasis and systemic features were present. The son died after 2 years of unresponsive continuously progressive disease. The father received pulses of high dose immunosuppressants that worked rapidly and prevented a life threatening course. These 2 cases illustrate the pathophysiologic hypothesis of Reiter's syndrome, emphasizing the role of environmental triggering factors and the relationship between spondylarthropathies in B27 positive patients. Fatal cases of Reiter's syndrome are very rare in the review of the literature.