The Lung Health Study (LHS) is a randomized clinical trial designed to determine whether a smoking intervention program and use of an inhaled bronchodilator (BD) can reduce the rate of decline of FEV1 in cigarette smokers with airflow limitation. During recruitment, spirometry was performed at second and third screening visits, a mean of 21 d apart. A total of 5,887 smokers, 35 to 60 yr of age and of whom 63% were men, met the study eligibility requirements. Smokers taking physician-prescribed BDs or with an FEV1 < 50% or > 90% predicted were excluded, as were those whose FEV1/FVC ratio was greater than 70%. Two inhalations of isoproterenol were given to determine BD response during the second visit. A serial dilution methacholine challenge test was done during the third visit to determine nonspecific airway reactivity. Ninety-five percent of the differences between FEV1 measured at the two visits were within 240 ml for women and within 320 ml for men (coefficients of repeatability). The best independent predictors of the mean short-term (between visit) intraindividual FEV1 variability were factors indicating intrinsic airway reactivity of the participants: bronchodilator response, methacholine reactivity, and the presence of wheezing; as well as factors influenced by the quality of spirometry testing: the difference between the highest and second highest FEV1s and peak flows during baseline spirometry, and the time to reach peak flow (PEFT).