To compare the efficacy of once daily monotherapy with that of standard combination antibiotic therapy for the initial management of patients suspected of serious bacterial infections, 105 patients were randomised to treatment with ceftriaxone alone (53 patients) or to a combination of cefuroxime and gentamicin (52 patients). There was no difference between the groups in proportions responding to therapy or proportions dying from infection, except when non-evaluable patients were excluded from the group with definite bacterial infection, in which case response was better among those treated with ceftriaxone. The groups did not differ in number of side-effects, but therapy had to be discontinued because of treatment failure, an adverse effect, or death in 1 of 53 patients given ceftriaxone and in 11 of 34 given the combination. Use of ceftriaxone was 107.36 pounds ($182.51) cheaper per patient, and saved 40 minutes of nursing and drug administration time per patient per day. Thus 2 g ceftriaxone given once a day is at least as effective and costs less in time and money than gentamicin plus cefuroxime for the initial treatment of patients with serious systemic bacterial infections.