The aim of this study was to define the within-subject variability for tests of respiratory function in patients with cystic fibrosis (CF) within the day, from day to day and from week to week. Twenty-eight patients with CF (aged 9-19 years) and 23 healthy height matched controls (aged 9-18 years) had measurements made of spirometry, lung volumes, maximal flows at three lung volumes and maximal inspiratory and expiratory pressures at the mouth. Testings were done on nine occasions, three times within a day, on consecutive days at one week intervals. Each individual's variability was summarized both as the within-subject coefficient of variation (WCV) and within-subject standard deviation (WSD). Means of WSD and median WCV are reported for both the patients with CF and normal subjects. The within-subject variability of VC, FEV1, TLC, RV, and RV/TLC was more appropriately assessed by the use of WSD rather than WCV. The WSDs in the CF group were significantly more variable (P less than 0.005) than in the normals for VC and FEV1. WCV best summarized within-subject variation for FEF25-75, FRC, V25, V50max and V75max for which the CF subjects were significantly more variable (P less than 0.005). Individuals' variability was very consistent, therefore assessment of significant change could be made more accurately by predetermining the variability of that individual, rather than using group data. We stress the importance to consider increased variability from day to day and week to week in the interpretation of change in lung function in patients with CF, and provide reference values for accurate interpretation of serial pulmonary function test results.