This study provides the first morphological evidence of significant structural damage following high doses of enflurane alone and confirms previous findings of transient renal functional abnormalities following high dosage enflurane. The study also indicates that enflurane may have a greater potential for renal toxicity in the presence of renal impairment. Treatment of Fischer 344 rats with a nephrotoxic dose of gentamicin prior to six hours of enflurane (GE) anaesthesia at 1 MAC resulted in increased serum concentration of the enflurance metabolite inorganic fluoride (GE, 43.9 +/- 1.5; E, 34.5 +/- 1.8 mu mol/L), increased urine flow rate and a greater degree of structural damage in renal proximal convoluted tubule cells than was observed with either gentamicin (G) or enflurane (E) alone. Treatment with gentamicin prior to enflurane also resulted in reduced urinary osmolality compared to enflurane or gentamicin alone (GE, 742 +/- 57; E, 1709 +/- 66; G, 985 +/- 32 m0sm/kg).