Fifty-nine children were enrolled in an open trial of aztreonam, a monocyclic beta-lactam, therapy for serious gram-negative infections. Thirty-six infections were microbiologically evaluable and received five or more days of therapy. Patients' ages ranged from 3 days to 12 years, and diagnoses included pyelonephritis or cystitis (20), deep soft tissue or joint infection (seven), septicemia (four), pneumonia (three), peritonitis, and epiglottitis. Causative bacteria included Escherichia coli and other Enterobacteriaceae, Pseudomonas aeruginosa, and Haemophilus influenzae. The standard regimen was 30 mg/kg every six or eight hours intravenously. All isolates were aztreonam-susceptible and were eradicated during therapy. Two patients had microbiologic relapses: a patient with Salmonella choleraesuis meningitis who was initially treated for only ten days and a patient with E coli pyelonephritis. Clinical cure was achieved in 31 of 36 children. Pharmacokinetic studies performed in six children demonstrated no difference in serum concentrations or pharmacokinetic variables between day 1 and day 7 of therapy. Although several patients had transient eosinophilia (eight), elevated levels of aminotransferase (seven), or thrombocytosis (ten), no clinically significant adverse effects were noted. In this initial, uncontrolled study, aztreonam was effective and safe in the treatment of a variety of serious gram-negative infections in children.