It is well documented that the severe hereditary disorder alpha 1-antitrypsin deficiency (alpha 1ATD) PiZZ is a strong risk factor for emphysema, especially among smokers, but the role of intermediate alpha 1ATD PiMZ and PiSZ in the development of emphysema remains uncertain. In this study, we have evaluated mortality and lung function of 94 persons with intermediate alpha 1ATD PiSZ of whom 66 were non-index cases, i.e. persons ascertained through family studies. The index cases and the non-index cases were similar with respect to sex, age and follow-up time, but differed in smoking habits and FEV1. Among the smokers there was no significant difference in pack-years between index cases and non-index cases. The overall Standardized Mortality Ratio (SMR) was 1.6 (95% confidence intervals (CI): 0.8-2.7). For the index cases the SMR was 4.3 (95% CI: 1.9-8.5) and for the non-index cases it was 0.8 (95% CI: 0.3-1.8). In the index group six patients died of pulmonary emphysema, one of pulmonary fibrosis, and one of colon cancer. In the non-index group two died of pulmonary emphysema, two of pneumonia, and one of cerebral haemorrhage. The mean initial FEV1% predicted among the index cases was 59% compared with 94% among the non-index cases. Based on the analysis of the non-index cases it is concluded that only a small fraction of persons with the PiSZ phenotype are at increased risk of developing pulmonary emphysema, and at an older age than persons with the PiZ phenotype.