The infection of the airways of cystic fibrosis patients by Pseudomonas aeruginosa is a complex, multistaged process that is associated with a deterioration of lung function. The complexity of the formation of biofilms and their interaction with the immune system means that treatment with antibiotics has been an uncertain science. Tobramycin nebuliser solution (TNS) is a novel formulation of the antibiotic tobramycin developed specifically for inhalation. A recent large trial comparing TNS with inhaled colistin provided an opportunity to define further the effect of antibiotic treatment on microbial infection. In the TNS group, the percentage of patients with a tobramycin minimal inhibitory concentration (MIC) > or = 4 mg l(-1) increased from 38 to 49%, and the percentage of patients with a colistin MIC > or = 4 mg l(-1) remained at 55%. In the colistin group, the percentage of patients with a colistin MIC > or = 4 mg l(-1) remained at 34%, whereas the percentage of patients with a tobramycin MIC > or = 4 mg l(-1) decreased from 27 to 16%. Furthermore, clinical and bacterial response to TNS and colistin was independent of the MIC at baseline. Neither antimicrobial therapy was associated with infection by Burkholderia cepacia or other inherently resistant pathogens. We conclude that conventional measures of antimicrobial resistance may underestimate the effectiveness of tobramycin and colistin when delivered at the high concentrations achieved with the TNS formulation.