Inactivation of aminoglycosides by carbenicillin and ticarcillin is a well-recognized in vitro phenomenon. Isolated case reports of in vivo inactivation of gentamicin by either carbenicillin or ticarcillin exist. We report a case of nearly complete in vivo inactivation of gentamicin by both ticarcillin and carbenicillin in the same patient. In the absence of either of the penicillin derivatives, the patient demonstrated predictable plasma concentrations and elimination characteristics of both gentamicin and tobramycin. As in previous reports, the interaction was intensified by high-dose carbenicillin-ticarcillin therapy in the face of underlying renal impairment. When using ticarcillin or carbenicillin along with gentamicin in renally impaired patients, special attention must be paid to both the gentamicin and carbenicillin-ticarcillin doses used and the plasma concentrations obtained.