A comparison of aztreonam and tobramycin was carried out in 49 hospitalized patients with lower respiratory tract infections caused by gram-negative bacilli. Patients were randomly assigned to the treatment drug. Clindamycin was given concomitantly until the pathogen was identified and the presence of a gram-positive microorganism was ruled out. Samples of sputum were obtained for culture from the lung parenchyma by deep expectoration or transtracheal aspiration. A pathogen was defined as an organism that showed heavy growth and predominated in the culture. Pseudomonas aeruginosa was the most frequently isolated pathogen, followed by Haemophilus influenzae and Proteus mirabilis. A variety of less common pathogens were represented. Thirty-five patients were treated with intravenous aztreonam (1-2 g every 8 hr) and 14 with intravenous tobramycin (3-5 mg/kg per day) until they were afebrile and sputum cultures had been free of the pathogen for 48 hr. The minimum duration of treatment was five days. In the aztreonam group, only two (5%) of the 37 gram-negative pathogens--one P. aeruginosa and one Escherichia coli--persisted. In the tobramycin group, seven (50%) of the 14 pathogens persisted. Clinical response paralleled microbiologic response. Adverse effects in both treatment groups were minor and transient. In this trial aztreonam was effective and safe for treatment of lower respiratory tract infections caused by P. aeruginosa and a variety of other gram-negative bacilli.