Between October 1980 and October 1981, cefotaxime plus amikacin were used in the treatment of 131 febrile episodes that occurred in 108 neutropenic patients with hematologic malignancies. The overall clinical response was 86.2%. Fevers of unknown origin and clinically or microbiologically documented infections responded in 88.8 and 84.4% of the cases, respectively. Renal toxicity occurred in 3.8% of the cases. In vitro studies showed that cefotaxime and amikacin were active against 78.7 and 94.7% of the pathogens, respectively, despite the high frequency (31%) of multiply resistant strains of Pseudomonas aeruginosa (defined as in vitro simultaneously resistant to carbenicillin, gentamicin, tobramycin and sisomicin) isolated from blood and infected sites. Synergy studies performed against 35 gram-negative bacilli isolated from blood revealed the presence of synergism between cefotaxime and amikacin in 54% of the cases. The peak levels of bactericidal activity in the serum of patients receiving cefotaxime plus amikacin showed median values of 1:128 and 1:8 against Escherichia coli and P. aeruginosa septicemias, respectively.