Ceftriaxone has a very long serum half-life and enhanced in vitro activity against common pediatric pathogens. Therefore we evaluated the efficacy and safety of once daily ceftriaxone therapy in 57 children with serious infections including: meningitis (26 patients); ventriculitis (3); pyelonephritis (7); osteomyelitis (6); abscess (4); septic arthritis (3); sepsis (2); and miscellaneous infections (6). The most common isolates were Haemophilus influenzae (23), Escherichia coli (9) and Staphylococcus aureus (8). Ceftriaxone was given intravenously or intramuscularly in a dose of 50 mg/kg for non-central nervous system (CNS) infections. Patients with CNS infections received an initial dose of 100 mg/kg followed by 80 mg/kg 12 hours later and once daily thereafter. In a limited number of patients no major differences in serum ceftriaxone concentrations were found after intravenous or intramuscular injection. Of 57 patients with pathogens isolated 55 were completely cured; in one patient with Klebsiella pneumoniae ventriculitis, intraventricular gentamicin was briefly added to the regimen. Another patient with an anaerobic liver abscess recovered after metronidazole was administered. In three patients a delayed response to ceftriaxone was noted. One patient with previous recurrent infections had a second episode of H. influenzae meningitis 22 days after cessation of therapy. Clinical side effects were noted in 10 of 71 patients (including 14 treated patients who had negative cultures). Seven patients had diarrhea, one each had fever or rash and one had fever, rash and arthralgia. Laboratory side effects in 16 of 71 patients included eosinophilia (7), thrombocytosis (7), elevated liver enzymes (4) and leukopenia and neutropenia (2).(ABSTRACT TRUNCATED AT 250 WORDS)