Infection is the leading cause of death in children with cancer. A retrospective review of 100 episodes of sepsis in 80 children with cancer for a 21-month period showed that 74% of isolates were Gram-positive bacteria. Coagulase-negative staphylococci were the most common pathogens, accounting for 35% of all isolates. Initial empiric antibiotic therapy of fever in neutrogenic cancer patients was piperacillin and tobramycin. All but 12% of the Gram-negative isolates were susceptible to one or both of the antibiotics. However, 31% of the Gram-positive isolates were resistant to both antibiotics and 38% of the coagulase-negative staphylococci were methicillin-resistant. All of the latter were susceptible to vancomycin. The increasing incidence of coagulase-negative staphylococci as causes of sepsis in cancer patients suggests that the choice of antibiotics for initial empiric therapy may need to include vancomycin or an antistaphylococcal penicillin depending on the local incidence of methicillin resistance.