Fifty-three hospitalized patients suffering from lower respiratory tract infections were evaluated in a randomized, comparative trial studying the safety and efficacy of ampicillin/sulbactam (2 g ampicillin plus 1 g sulbactam intravenously every 6 h) versus cefotaxime (2 g intravenously every 6 h). Thirty-four of the 36 and 16 of the 17 patients treated with ampicillin/sulbactam and cefotaxime, respectively, were evaluable. Clinical and bacteriologic efficacy did not differ significantly between the two treatment groups (p = 0.828 and p = 0.648, respectively). Twenty-one (61.8%) of the ampicillin/sulbactam-treated patients were cured, eight (23.5%) improved and four (11.8%) were treatment failures. Nine (56.3%) of the cefotaxime treated patients were cured, four (25.0%) improved and two (12.5%) failed therapy. All primary pathogens were eradicated in 19 (55.9%) of the ampicillin/sulbactam group and were partially eradicated in seven (20.6%) patients. In the cefotaxime treatment group bacteriologic eradication occurred in 10 (62.5%) and partial eradication in two (12.5%) patients. Both study drugs were well tolerated, as the number of adverse reactions in each treatment group was small and similar between the two groups. Ampicillin/sulbactam appears to be as safe and effective as cefotaxime in the therapy of hospitalized patients with lower respiratory tract infections caused by beta-lactamase positive and beta-lactamase negative pathogens.