Twenty-seven patients with cystic fibrosis and endobronchial colonization with Pseudomonas aeruginosa were randomly assigned to inhale either 2 mL saline (12 patients) or 80 mg tobramycin solution (15 patients) 3 times daily. One control patient died; all others completed the study (mean duration 32 months). No significant differences were found between the two groups at enrollment. The treatment group showed no change, while the control group had a significant decline in both pulmonary function and clinical status over the study period. Individually, 11 of 12 patients in the control group showed deterioration, while 9 of 15 in the treatment group with susceptible P. aeruginosa at enrollment acquired resistant organisms. There was no evidence of significant nephro- or ototoxicity. Although inhaled tobramycin appeared to arrest the decline in pulmonary status, further work is required to identify patients most likely to respond.