The fluoroquinolones represent a new class of antimicrobial agents with a broad spectrum of activity. We report three cases of acute renal failure following ciprofloxacin in patients without a previous history of renal insufficiency. The average baseline creatinine was 1.1 mg/dl and rose to an average of 4.0 mg/dl during therapy. The length of antecedent ciprofloxacin therapy ranged from several days to several weeks. Other causes of acute renal failure and postobstructive uropathy were excluded. Kidney size was normal-to-increased. Gallium scans were positive in one of two patients studied. Peripheral eosinophilia developed in one case, suggesting an acute hypersensitivity reaction to the drug. The acute renal failure in all cases was non-oliguric and was completely reversed after discontinuation of ciprofloxacin. In two of the three reported cases there was an increased creatinine to BUN ratio, but increased production of creatinine (i.e., rhabdomyolysis) was unlikely with a normal serum creatinine phosphokinase (CPK). In addition, we performed in vitro studies which eliminated the possibility of methodological artifact. The nephrotoxicity of the quinolones has been linked to the development of crystalluria in experimental animals. However, in humans, crystalluria is unlikely and renal damage has not been noted. There have been only two previous case reports of acute renal failure due to oral ciprofloxacin therapy. In one, biopsy showed acute interstitial nephritis. We conclude that oral ciprofloxacin therapy may lead to acute renal failure secondary to tubulointerstitial nephritis characterized by an increased creatinine to BUN ratio. Patients placed on ciprofloxacin therapy need to be followed closely.