A randomized, placebo-controlled, multicenter trial evaluated the safety and efficacy of 300 mg aerosolized tobramycin solution for inhalation (TSI) administered twice daily for 4 weeks in 74 bronchiectasis patients colonized with Pseudomonas aeruginosa (PA). Patients were evenly divided between TSI therapy and placebo. After 2 weeks of treatment, patients treated with TSI had a mean reduction in sputum PA density of 4.8 log(10.) This reduction was maintained for the duration of treatment. The placebo group showed no change in PA density during the study. Two weeks after the end of therapy, PA had been eradicated in 13 TSI-treated patients. PA was not eradicated in any placebo patients. Among those colonized with Staphylococcus aureus at baseline, 6 of 9 patients in the TSI group and 2 of 9 patients in the placebo group were culture negative for this organism 2 weeks posttreatment. Sixty-two percent of TSI-treated patients were judged by a physician as having an improved general health status, compared with 38% of placebo-treated patients. Dyspnea, wheezing, and chest tightness were reported more frequently in the TSI-treated patient group than in the placebo-treated patient group.