Previous estimates of survival of patients with alpha-1-antitrypsin deficiency (alpha 1ATD) have been based on selected patients. In this paper we have compared the survival of 397 patients with severe alpha-1-antitrypsin deficiency either ascertained because of pulmonary impairment (index cases) or ascertained through family studies (non-index cases). The patients were drawn from the nationwide Danish alpha 1ATD register. The overall median survival was 54.5 years with no significant difference between males and females. Survival for index cases was less than for the non-index cases regardless of smoking history (49.4 years and 69.3 years respectively). When we analyzed index cases and non-index cases separately there was no difference between the survival of smokers and never-smokers in the index group. In the non-index group smokers had a shorter survival than never-smokers. The survival of non-index never-smokers was similar to the survival of the normal Danish population. We conclude that the prognosis of severe alpha 1ATD is better than previously assumed, and that although smoking is a major risk factor the development of emphysema in patients with severe alpha 1ATD is multifactorial.