To assess the role of smoking and heterozygous (PiMZ) alpha 1-antitrypsin deficiency as risk factors in the pathogenesis of emphysema, we compared results of FEV1.0 (and FEV%) measurements in a random population sample of 56-year-old men with those obtained in an investigation 6 years earlier. We studied 32 PiMZ heterozygotes (14 smokers) and 31 PiM controls (13 smokers), representing 81% of the initial series. The annual decline in FEV1.0 values in non-smoking 56-year-old PiMZ men did not differ from PiM controls (smokers or non-smokers). In contrast, smoking heterozygotes showed a significantly higher mean annual decrease in FEV1.0 than non-smoking heterozygotes (75 ml and 40 ml/year respectively). In spite of this evidence of a modest accelerating effect on lung ageing among smoking PiMZ subjects during the 6 years covered by the study, no increased prevalence of clinical obstructive lung disease was noted.