Results from longitudinal and cross-sectional studies of pulmonary function are often compared. However, previous studies in adults suggest that results from longitudinal and cross-sectional studies are different and may not be comparable. In order to evaluate these differences further, prospectively collected data in a group of children were analyzed by both longitudinal and cross-sectional methods. Spirometry was performed longitudinally over a period of 8 years on 58 healthy children. Straight-line regressions of expiratory flow-volume parameters on height were computed by averaging the individual regression lines for each child. A cross-sectional sample from these same children was analyzed and compared to the longitudinal analysis. For all expiratory flow-volume parameters, the cross-sectional analysis resulted in a significantly greater increase in growth with increasing height than the longitudinal analysis (P less than 0.005 for slope for all parameters except PEFR, P less than 0.05 and Vmax75, P less than 0.01). These differences cannot be explained by learning or horse-racing effects, loss to follow-up, or regression to the mean; however, they could be explained by cohort changes, time trends of pulmonary function, differences in the weighted averages used in the two analyses, or incorrect modeling. These observations indicate that comparisons between cross-sectional and longitudinal investigations must be made cautiously. These data do not support many of the reasons suggested for the differences in previous reports. It is recommended that studies of pulmonary function use a control group and investigate the groups at the same time and in the same manner.