One hundred thirty-three febrile episodes in 115 neutropenic patients with hematologic malignancies were empirically treated with ceftriaxone and amikacin in a single daily dose. An indwelling central venous catheter (CVC) was present in 44 cases. Septicemia was documented in 18 (41%) patients with CVC (13 gram-positive, 5 gram-negative and 1 fungus) and in 30 (34%) patients without CVC (19 gram-positive, 10 gram-negative and 2 fungi). Coagulase-negative staphylococcus was observed in 10 out of 19 blood isolates in the presence of a CVC and in 6 out of 31 blood isolates in patients without CVC. Empiric therapy was successful in 56.4% of cases. Improvement after the addition of vancomycin or teicoplanin was observed in 38.6% of cases with a CVC and in 13.5% of those without (p less than 0.02). Only two patients died from gram negative septicemia, and the substitution of ceftriaxone with another beta-lactam was necessary in only 6% of the cases. Empiric therapy with single daily-dose ceftriaxone and amikacin appears to be effective in febrile neutropenic patients; our data, however, show the high incidence of Staphylococcus epidermidis septicemia and the frequent need to add an anti-gram-positive drug in patients with an indwelling CVC.