This study investigated the determinants of sex-specific maximally attained levels of FEV(1), VC, and the ratio of FEV(1) to VC. Subjects were between the ages of 15 and 35 years (1,818 males and 1,732 females), participating in the Vlagtwedde/Vlaardingen study in The Netherlands. The subjects were followed (3-year intervals) with questionnaire, spirometry, peripheral blood eosinophil counts, and testing for airway responsiveness to histamine. Skin tests were performed only at study onset. Regression splines were used to assess the effects of these variables on levels of FEV(1), VC, and the ratio of FEV(1) to VC, with adjustment for age, height, and area of residence. Current (-44 ml/pack/day) and cumulative (-85 ml/10 packs/year) cigarette smoking were significant predictors of reduced maximal level of FEV(1) in males but not in females. The presence of respiratory symptoms (-114 ml in males, -106 ml in females), increased eosinophils (-128 ml [males], -53 ml [females]), and increased airway responsiveness (-225 ml [males], -213 ml [females]) were all significant predictors of reduced level of FEV(1). To the degree that these factors diminished plateau phase pulmonary function, they may be important predictors of chronic obstructive pulmonary disease in later life.