Profoundly granulocytopenic patients in whom fever develops are likely to have gram-negative septicemia, which may rapidly be fatal. These patients require early empiric therapy with a synergistic bactericidal combination of antibiotics that should be chosen on the basis of in vitro studies, animal models, and results of volunteer and clinical trials. From in vitro studies, it is apparent that the degree of synergy between an aminoglycoside and a beta-lactam is determined mainly by the aminoglycoside. Amikacin is the most synergistic of the aminoglycosides. A combination of an aminoglycoside such as amikacin plus a beta-lactam active against Pseudomonas is probably still the best empiric therapy available. The newer compounds and beta-lactam combinations still have to be proven effective in the clinical setting of the persistently and profoundly granulocytopenic patient with fever and bacteremia.