A prospective study of 100 pediatric patients (2 months to 17 years of age) who had malignancies and fever was conducted. Gentamicin or netilmicin and a beta-lactam antibiotic were administered as initial empiric treatment. Before therapy profound granulocytopenia (fewer than 500 polymorphonuclear leukocytes/Til) was present in 66% of children and persisted to the end of therapy in 42% of children. Of the 40 children with microbiologically documented infections, 38 (95%) responded to therapy. The aminoglycoside dosing regimen of 2 mg/kg/dose intravenously over 60 minutes every 6 hours produced antibiotic concentrations in serum of 5.8 ± 0.3 μg/nil at the end of the infusion in the netilmicin group and 1.5 ± 0.1 μg/ml 6 hours after the infusion and of 6.2 ± 0.2 and 0.9 ±0.1 μg/ml for the two time periods in the gentamicin group. The serum half-lives, volumes of distribution and the total body clearance rates were comparable for netilmicin and gentamicin. No accumulation of netilmicin or gentamicin was noted. Seven patients had renal compromise, five before institution of antibiotic therapy and two while on therapy. Four episodes of ototoxicity were not related to antibiotic therapy. Superinfection occurred in five children. The combination of either gentamicin or netilmicin with a beta-lactam antibiotic produced excellent results for episodes of fever in neutropenic children with cancer. In children with severe underlying disease and/or granulocytopenia, antibiotic combinations have achieved an optimal efficacy. Future emphasis should be placed onprevention, immunoregulation and nonbacterial pathogens.