The Chemotherapy Alliance for Neutropenics and the Control of Emerging Resistance Program (CANCER) monitored the susceptibility of pathogens recovered in hematology/oncology centers from 2000 to 2002. A total of 3970 isolates from 32 hospitals (26 United States, 6 Canada) were analyzed at a central location (JMI Laboratories, North Liberty, IA) for trends in pathogen occurrence and reference antimicrobial susceptibility profiles. The top 5 ranking pathogens were Staphylococcus aureus (19.3%), coagulase-negative staphylococci (CoNS) (14.1%), Escherichia coli (13.4%), Enterococcus spp. (10.2%), and Klebsiella spp. (9.5%). A total of 35.5% of S. aureus and 78.8% of CoNS were resistant to oxacillin, whereas 22.0% of Enterococcus spp. were resistant to vancomycin. E. coli and Klebsiella spp. were highly susceptible (>90%) to piperacillin/tazobactam, 3rd-generation cephalosporins, and ciprofloxacin, but 3.9% and 2.4% of these species, respectively, met screening criteria for extended spectrum beta-lactamase production. Enterobacter spp. were less susceptible to piperacillin/tazobactam, ceftazidime, and ceftriaxone (83.7-88.2%) because of Amp C production and were most inhibited by cefepime and imipenem. Amikacin and polymyxin B were very active against Pseudomonas aeruginosa (97.4-97.7% susceptible). Prevalence of S. aureus, E. coli, Enterobacter spp., and Klebsiella spp. increased significantly (+48% to 98%) with age, whereas CoNS and viridans group streptococci decreased markedly (-62% to 69%) with advancing age. The isolation of Gram-positive pathogens declined (55% to 47%) with age (< or =14 to > or =65 years). Fluoroquinolones generally exhibited decreased susceptibility with increased age against nearly all listed pathogens. Oxacillin resistance rates for S. aureus increased with age (6-46%) as did vancomycin resistance rates for enterococci (nil in < or =14 years group to 18-24% in adults). Pathogens infecting neutropenic patients did not reflect greater resistance than those found in the general hospitalized patients. Gram-positive organisms were only slightly more predominant (53.4%), and cited age-related variations in pathogen occurrence and/or susceptibility patterns by species must be considered for empiric regimes for hematology and oncology patients.