The Ear, Nose, and Throat department of the Meir Hospital treated 91 patients with malignant external otitis during the past 16 years. The last 23 patients with malignant external otitis were treated with ciprofloxacin 750 mg twice daily, combined with local excision of the aural lesion. The records of 61 of our previous 68 patients who underwent surgery and were hospitalized and treated with an intravenous extended-spectrum penicillin and gentamicin for six to eight weeks, were analyzed. Twenty-one of 23 patients treated with ciprofloxacin were cured; therapy failed in two patients. Treatment averaged 16.8 days of hospitalization, and bacteriologic eradication was achieved after an average of 7.04 days, as compared with 49 and 15.3 days, respectively, in the group of patients with the intravenous treatment. The mean peak concentrations of ciprofloxacin in serum varied between 2.5 and 3.7 micrograms/ml, and the drug concentrations in different ear tissues were 0.2 to 13 micrograms/g. The treatment with ciprofloxacin was well tolerated with no significant side effects, whereas serious side effects were noted in 45.9 percent of the previous intravenously treated group. The concentrations of the drug in serum and ear tissues were higher than the average minimal inhibitory concentration for Pseudomonas aeruginosa. Use of ciprofloxacin treatment, combined with local excision of the aural lesion, will bring about healing of malignant external otitis in the majority of cases. Ciprofloxacin can be given on an ambulatory basis after a relatively short period of hospitalization.