Airway reactivity is associated with rapid decline in pulmonary function with age or packyears of smoking in otherwise normal subjects. Because heterozygotes for cystic fibrosis (CFHZ) have a higher prevalence of airway reactivity than do controls, we tested the hypothesis that CFHZ have a more rapid decline in pulmonary function with age or packyears of smoking than do controls. We performed spirometry on 280 parents of children with CF and 280 age-matched control parents of children with heart disease. The ALA-DLD-78 questionnaire was also administered to these volunteers. Although the CF parents report wheezing apart from a cold more frequently than control parents, they show no greater decline of pulmonary function (FEV1, FEF25-75%, or FEV1/ht3) with age or packyears of smoking than do controls. The complaint of wheezing apart from a cold contributes significantly to the variance of FEV1 and FEF25-75% even when the effects of height, age, packyears of smoking, sex, and CF heterozygosity are controlled. The hypothesis that obligate heterozygotes for CF have increased age- or smoking-related decline in airflow is not supported by these data. Instead, the results suggest that any pulmonary function abnormalities associated with CF heterozygosity are small and not clinically significant and that CF heterozygosity per se is not a major risk factor for development and progression of obstructive airways disease.