It has been established that inhaled tobramycin has a positive effect on respiratory function in Pseudomonas-aeruginosa positive patients with cystic fibrosis (CF). In a previous study the authors reported that low-dose tobramycin preparations containing the preservative phenol caused significant bronchial obstruction. Recently, high-dose tobramycin preparations with and without preservatives/phenol have become available. To assess the airway response to these preparations flow/volume curves in 12 patients with CF (four males, eight females, mean age+/-SD=19.0+/-7.4 yrs) were measured. The tobramycin preparations: Nebicina 2.0 mL (150 mg, containing the preservative phenol), Distobram 3.0 mL (150 mg, containing preservatives), Tobi 5.0 mL (300 mg), Tobi 2.5 mL (150 mg), and Tobi 5.0 mL, were used after bronchodilator application. Immediately and/or 5 min after the tobramycin inhalations there was a significant fall in lung function with the different preparations. There was no significant difference between preparations with and without preservatives/phenol. The bronchial obstruction was comparable to that observed after the inhalation of low-dose tobramycin and after saline. After 10 min of inhalation, the lung function returned to baseline values. Most patients preferred the Tobi 2.5 mL and disliked the Nebicina preparation due to the unpleasant taste. Preceding treatment with bronchodilators prevented the decline in lung function. Assessment of bronchial response at the first nebulisation of high-dose tobramycin and, in case of significant obstruction, beta-agonists in combination with the antibiotic inhalation are recommended.