Cefsulodin sodium is a narrow-spectrum cephalosporin with marked in vitro activity against clinical isolates of Pseudomonas aeruginosa. We have studied the antibiotic in a clinical trial in 10 patients admitted to the Pediatric Ward of the University of Virginia Medical Center with cystic fibrosis and recurrent acute lower respiratory tract infections with P. aeruginosa isolated from their sputa. The patients received 500 to 1,500 mg of cefsulodin every 6 hours by intravenous infusion for 10 to 22 days. Mean peak drug levels in plasma after 500, 1,000, and 1,500 mg were 46, 71, and 90 micrograms/ml, respectively, and the mean minimal inhibitory concentration of all organisms was 7.5 micrograms/ml. Detectable levels of cefsulodin in sputa were found in approximately half of the random samples and ranged from 2 to 5 micrograms/ml. The clinical response was satisfactory in nine (90%) of the patients. One patient gained weight and had improved pulmonary function tests but showed no reduction in sputum production and no improvement in arterial blood gas values. In pulmonary function tests, four of five patients tested showed an average 43% increase in forced vital capacity after initiation of therapy and five of five had an average 51% increase in forced expired volume in 1 s. No adverse effects were observed.