Ceforanide is a new (parenteral) long-acting cephalosporin with antimicrobial activity comparable to those of other second-generation cephalosporins. In a randomized prospective study, patients with community-acquired bacterial pneumonia were treated with ceforanide at 0.5 g every 12 h (28 cases) or with cefazolin at 1.0 g every 8 h (26 cases). The study groups were comparable in clinical and laboratory findings, including etiological diagnosis. Streptococcus pneumoniae was isolated from the sputum of 38 patients, of whom 8 (21%) were bacteremic. Mean peak and trough serum levels of ceforanide drawn 1 and 11.5 h after the 0.5-g intravenous dose were 39.6 and 2.5 microgram/ml, respectively. Of the 50 patients evaluable for efficacy, all responded clinically with no serious adverse reactions. In spite of clinical improvement and in vitro susceptibility, Haemophilus influenzae persisted in the sputum of five of the eight cefazolin-treated patients and four of the five patients treated with ceforanide. Ceforanide appears to be as safe and effective as cefazolin for the therapy of pneumonia caused by S. pneumoniae or H. influenzae, but neither drug was effective in clearing H. influenzae from the sputum.