Strains of Pseudomonas aeruginosa resistant to clinically relevant antibiotics (beta-lactams, quinolones, aminoglycosides) were detectable in sputa of cystic fibrosis patients. Correlations between in vitro susceptibility and bacteriological results in vivo were demonstrated at a quantitative level. P. aeruginosa strains susceptible prior to antibiotic therapy were observed to become resistant towards each of the compounds used for treatment. We conclude that antibiotic therapy in cystic fibrosis has to be optimized by culture specific selection of the drugs and consecutive bacteriological follow-ups.