Intravenous (IV) antibiotic therapy with a combination of ticarcillin disodium and sulfamethoxazole-trimethoprim was administered as initial empiric treatment of 218 febrile episodes in patients with cancer. Seventy-nine (77%) of 102 episodes of infection were cured, and the temperature returned to normal in 88 (74%) of 199 febrile episodes without proved infection. The response rates for the major sites of infection were as follows: septicemia, 89%; pneumonia, 52%, soft-tissue infections, 85%; and urinary tract infections, 100%. The cure rate of Gram-negative aerobic bacillary infections was 87%. No significant influence of initial neutrophil count on response rate was noted, although patients in whom the neutrophil count increased during therapy had a higher response rate (84%) than patients in whom the neutrophil count decreased or remained stable (72%). The combination of ticarcillin and IV sulfamethoxazole-trimethoprim is satisfactory initial empiric antibiotic therapy for febrile episodes in neutropenic patients with cancer.