Fifty-three infants and children, aged three months to 15 years, were treated with an average daily dose of 100 mg of cefamandole/kg intravenously. Of these patients, 47 had soft tissue cellulitis and six had pneumonia. Primary pathogens, including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae, were isolated from 43 of the 53 patients. Bacteremia was documented in six of the 53 patients. A satisfactory clinical and bacteriologic response to cefamandole was achieved in all cases except on (98%). The only treatment failure occurred in an infant with both periorbital cellulitis and bacteremia due to H. influenzae who developed meningitis while receiving cefamandole; no extravasation of the drug across the blood-brain barrier could be detected in spite of inflamed meninges. In general, the only aberrant effects of cefamandole were the appearance of eosinophilia in 28% of patients and a positive indirect Cooms' test without hemolysis in one patient. Cefamandole showed excellent in vitro activity against 87 ampicillin-resistant strains of H. influenzae. Because it has greater activity than any of the other cephalosporins against this important pediatric pathogen, cefamandole may have particular pertinence in the treatment of infections in infants and young children.