The antibiotic resistance of Klebsiella pneumoniae isolates from 12 medical centers worldwide, over a 1- to 6-year period, were tested. Clinical isolates of K. pneumoniae were resistant to ampicillin and carbenicillin. Resistance to other antibiotics was less frequent with isolates of K. pneumoniae from 5 of 6 US centers than with those from 6 centers outside the US. In nearly all of the centers, resistance to sulfamethoxazole-trimethoprim, gentamicin, tobramycin, or chloramphenicol was more frequent in isolates of K. pneumoniae than in those of Escherichia coli, while the reverse was true for resistance to tetracycline. Resistance to multiple antibiotics declined gradually in isolates of K. pneumoniae at one center, but rose abruptly again with dissemination of a new plasmid.