We report a multicentric, open trial of intravenous followed by oral ofloxacin, 400 mg every 12 h, as therapy for 100 cases of nosocomial pneumonia and community-acquired pneumonia requiring hospitalization. The typical subject was 57 yr old, and underlying diseases, such as chronic obstructive pulmonary diseases (COPD), diabetes mellitus, and congestive heart failure, were common. For 10 subjects previous therapy had failed. There were 118 pathogens isolated in blood or sputum; S. pneumoniae was the most common (42), followed by H. influenzae (13), Klebsiella spp. (11), and S. aureus (10). Ofloxacin was administered for an average of 5.7 days intravenously followed by 6.9 days orally. Response to therapy was judged to be cure in 71 subjects, improvement in 24, and failure in 5. Among the more seriously ill subjects, ofloxacin therapy was successful for four of five immunocompromised subjects, for 12 of 12 subjects with nosocomial pneumonia, three of whom were on the ventilator, and for nine of 10 subjects with community-acquired pneumonia and bacteremia, including seven of eight cases due to S. pneumoniae. Univariate risk factor analysis revealed underlying COPD and/or tachypnea upon admission to be associated with failure of ofloxacin therapy, with bacteremia suggestive of failure. Conversely, ofloxacin was equally effective in cases in whom previous therapy failed and in cases of nosocomial pneumonia, multilobar pneumonia, and/or pneumonia due to S. pneumoniae. Results for P. aeruginosa were inconclusive. Intravenous followed by oral ofloxacin was highly effective in many difficult cases of pneumonia.