The use of cefaclor advanced formulation (cefaclor AF) in the treatment of pneumonia caused by susceptible organisms was investigated in a multi-center trial conducted in the United Kingdom and the United States. A total of 266 patients were enrolled in this double-blind, double-dummy, randomized, parallel study; 132 patients were treated with cefaclor AF and 134 patients received the reference drug cefaclor. Inclusion criteria were a diagnosis of lobar pneumonia or bronchopneumonia, with a positive sputum culture and an infiltrate on chest roentgenogram. Patients received either cefaclor AF (750 mg twice daily) or cefaclor (500 mg three times daily) for 10 to 14 days. Forty patients in the cefaclor AF group and 45 in the cefaclor group were evaluable for efficacy, with 37 (92.5%) and 43 (95.6%), respectively, showing a favorable posttherapy clinical response. Proven or presumed pathogen elimination was achieved in 87.5% and 86.7% of cases, respectively. Both study drugs demonstrated high levels of activity against Streptococcus pneumoniae, Haemophilus influenzae (including beta-lactamase-producing strains), and Moraxella catarrhalis (including beta-lactamase-producing strains). There were no statistically significant differences between drugs in efficacy results. One or more side effects were reported by 42.4% of the patients treated with cefaclor AF and by 44.0% of those treated with cefaclor; diarrhea, nausea, headache, and respiratory disorders were the most common adverse events. No drug-related side effects were seen with a frequency or severity that would be unexpected with the use of oral cephalosporins. Cefaclor AF and cefaclor performed equally well with respect to clinical and bacteriologic response rates in the treatment of pneumonia.