To evaluate the sensitivity of high-resolution computerized tomography (HRCT) of the chest compared to spirometry measures in evaluating the effects of tobramycin solution for inhalation (TSI) in cystic fibrosis (CF) patients.Thirty-two subjects >/=6 years old with mild to moderate CF lung disease were enrolled in a randomized, double-blind, placebo-controlled pilot study. Duration was 28 days; 31 subjects completed the study.HRCT scores decreased 4.06 +/- 3.20 (mean +/- SD) for TSI and decreased 0.17 +/- 1.78 for placebo subjects (P = 0.13). Mean forced expiratory flow during middle half of forced vital capacity (FEF(25%-75%)) predicted increased 6.08 +/- 4.86 for TSI and decreased 0.60 +/- 2.34 for placebo (P = 0.23). Percentage forced expiratory volume in 1 s (FEV(1)) predicted increased slightly for both TSI and placebo (1.29 +/- 3.33 for TSI and 1.17 +/- 1.4 for placebo) (P = 0.97). Two of eight HRCT component scores (atelectasis and inhomogeneity) were observed to be highly discordant with observed HRCT global total score and other HRCT component scores. A modified total score was calculated by dropping them from the global total score. The modified HRCT total scores decreased 6.68 +/- 3.09 for TSI subjects and increased 0.02 +/- 2.0 for the placebo subjects (P = 0.07). Sample sizes were calculated to show statistical significance by differences in modified total HRCT scores, global total HRCT scores, FEF(25%-75%) predicted or FEV(1) % predicted. A total of 60, 100, 200, and over 800 patients would be necessary respectively.HRCT can be a useful measure of change in CF pulmonary disease, requiring a smaller sample size than that required to show treatment effect by pulmonary function testing (PFT) alone.