During prophylaxis with gentamicin and amoxicillin following surgical repair of a meningomyelocele in a newborn infant, a cerebrospinal fluid leak occurred and fever ensued. Cultures of ventricular fluid yielded Serratia marcescens resistant to several antibiotics, including gentamicin and tobramycin, but sensitive to amikacin. When therapy with amikacin was substituted for that with gentamicin and amoxicillin, cultures yielded an additional colony type of S. marcescens, which was antibiotic-sensitive but of the same serotype as the original isolate, that eventually replaced the original resistant organism. The resistant S. marcescens was shown to possess a 105 X 10(6)-dalton plasmid not observed in the sensitive variant. The sensitive variant may have originated by loss of the plasmid from the resistant organism, possibly by removal of the selection pressure of antibiotics, which favored the emergence of a bacterial population that did not harbor resistance plasmids during clinical therapy.