The recommended treatment for gonorrhoea in the United Kingdom has, until recently, included the fluoroquinolone, ciprofloxacin, which consequently was used by most genitourinary medicine clinics. In 2002 national surveillance data showed that resistance to ciprofloxacin had risen to a prevalence of 9.8% (9% in 2003), indicating that the target of >95% efficacy in first line therapy was no longer achievable. The third generation cephalosporins, ceftriaxone (intramuscular) or cefixime (oral), are the recommended alternatives, but recent audit data reveal other cephalosporins are currently being used to treat gonorrhoea, notably including cefuroxime (intramuscular or, often, oral). A pharmacodynamic analysis was undertaken to determine whether all these regimens were equally potent. Ceftriaxone, 250 (or 500) mg intramuscularly, or cefixime, 400 mg orally, were calculated to give free drug concentrations above the MIC90 for 22-50 hours post dose whereas the cefuroxime regimens being used were pharmacoctynamically borderline, achieving this target for only 6.8-11.2 hours and raising the spectre that continued use may select for stepwise increases in resistance, as occurred with penicillin. We therefore underscore that ceftriaxone or cefixime should be the agents of choice to replace ciprofloxacin, as recommended in the new treatment guidelines, and that cefuroxime is a poor substitute.