The aim of this study was to investigate the possibility of a drug-drug interaction between ciprofloxacin and fennel (Foeniculum vulgare) in a rat model. Pharmacokinetic assessment of ciprofloxacin was performed in two groups of male Sprague-Dawley rats. One group (n = 5) received 20 mg kg(-1) antibiotic orally with concomitant oral dosing of the aqueous fennel extract (2 g herb kg(-1)) whereas the controls (n = 5) received 20 mg kg(-1) oral ciprofloxacin. Blood and urine samples were collected over 6 and 24 h, respectively, for quantitation of ciprofloxacin by HPLC. A non-compartmental model was employed for pharmacokinetic analysis. Major ingredients and metal cations in the fennel extract were determined. Compared with the control, maximum plasma concentration, area under the curve and urinary recovery of ciprofloxacin were significantly (P < 0.05) lower, by 83, 48 and 43%, respectively, in rats receiving concomitant dosing of the two agents. The relative bioavailability of ciprofloxacin, under the influence of fennel, was estimated to be 0.52. In addition, its apparent volume of distribution and terminal elimination half-life were significantly (P < 0.05) increased, from 30.8 +/- 11.1 (L kg(-1)) and 2.0 +/- 0.4 (h) to 143.8 +/- 31.6 (L kg(-1)) and 5.2 +/- 2.0 (h), respectively. Although none of the organic components of fennel seemed to cause this interaction, the total amount of ten metal cations measured was found to be 13 mg g(-1). Significant interaction between ciprofloxacin and fennel was observed in this study. Absorption, distribution and elimination of ciprofloxacin were all affected. These changes might be because of the formation of a more lipophilic ciprofloxacin chelate in the presence of relatively large amounts of metal cations. If, therefore, the two therapeutic agents are used concurrently, an adequate dosing interval is needed to ensure the efficacy of ciprofloxacin.