The efficacy and safety of parenteral ofloxacin were evaluated in an open, multicenter study of hospitalized patients with pyelonephritis. The patients received ofloxacin 400 mg IV as an initial dose followed by ofloxacin 200 mg IV b.i.d. for a minimum of three days. The patients could then continue ofloxacin orally 200 mg b.i.d. for a total of seven to fourteen days. The most common pathogens isolated were Escherichia coli, Enterobacter cloacae, and Klebsiella pneumoniae. Microbiologic eradication was achieved in 65 of 66 evaluable patients (98%), and clinical cure or clinical improvement was noted in all patients. Of 82 patients evaluable for safety, 12 (15%) reported drug-related adverse events, the most frequent of which was pruritus or rash. None of the patients experienced drug-related central nervous system symptoms. Ofloxacin is well tolerated and highly effective in the treatment of pyelonephritis.