Gram-negative pneumonia is a frequent complication in hospitalized patients, particularly in those with diminished defenses. The severity of the infections makes it necessary to start immediately an empirical antimicrobial therapy that usually combines a broad-spectrum β-lactam antibiotic with an aminoglycoside (AMG), despite the potential toxicity of this regimen. We have compared the efficacy of a new β-lactam antibiotic, aztreonam, which shows both a specific spectrum of activity against gram-negative bacteria and a very good diffusion into pulmonary tissue, with that of another antibiotic regimen including an AMG. Of a total of 69 patients, 43 were treated with aztreonam and the remaining patients with an AMG. Both groups were comparable with respect to the severity of infection and underlying pathology. Clinical efficacy was similar in the two regimens (81% aztreonam, 62% AMG). However, antimicrobial efficacy was superior in the aztreonam group (88% aztreonam, 65% AMG), although differences disappeared in patients treated with the combination amikacin + cefotaxime or ticarcil-lin in the AMG group. Colonization/superinfection was also similar in both groups, although the selection of gram-negative bacteria occurred more frequently in the AMG group. Our results suggest that aztreonam, in monotherapy, may be a useful alternative for the treatment of gram-negative pneumonia.