For fifteen years oral ciprofloxacin has been the standard treatment for malignant otitis externa, a sometimes fatal osteomyelitis of the skull base usually caused by Pseudomonas aeruginosa. Resistance to ciprofloxacin is developing. Over a 16-month period, we saw five cases where malignant otitis externa progressed, with the development of cranial nerve palsies in four cases, despite oral ciprofloxacin. Prolonged intravenous antibiotic therapy became necessary. One case was managed largely as an out-patient, but four patients spent many weeks in hospital. Only two cases had diabetes and this was monitored and controlled. Pseudomonas aeruginosa was isolated in four of the five cases, but antibiotic sensitivity to ciprofloxacin was not determined. In one case a later isolate was tested and found to be ciprofloxacin resistant. Progress was monitored by serial C-reactive protein (CRP) and white cell count. For diagnosis and assessing response to treatment we considered serial magnetic resonance imaging or computed tomography more useful than isotope bone scan. There must be a readiness to use intravenous antibiotics, as a response to ciprofloxacin can no longer be assumed. Bacterial isolates must be tested for sensitivity to antibiotics including ciprofloxacin, and further biopsy and culture are essential if treatment fails.