To assess the renal effects of fluoride, isolated rat kidneys were perfused in single pass mode for 120 min. Five, 15 and 50, as well as 150, 500 and 1500 mumol NaF were administered 60, 80 and 100 min after starting the perfusion, respectively. Kidneys were perfused with constant pressure (100 mmHg). The perfusate consisted of a substrate supplemented Ringer solution containing hydroxy ethyl starch (HES) to produce isoncotic conditions. Concentrations below 500 mumol/l NaF did not induce major changes in the main parameters of renal function. Only upon admixture of the highest concentration of 1500 mumol/l NaF severe changes in renal function could be observed, resulting in complete anuria and a drastic reduction of renal perfusion to 5% of control, associated with a cessation of glomerular filtration. Due to the lack in tubular load, tubular reabsorptive processes inevitably declined to zero. The morphological analysis of kidneys exhibited to 500 mumol/l NaF revealed the occurrence of vesicular material within the urinary space. These vesicles could electron microscopically be identified as membrane enclosed material of podocytic origin. The interstitium was widened. Upon admixture of 1500 mumol/l NaF, kidneys responded with a decrease of the interstitial space. Moreover, epithelial cell swelling, hydropic degeneration of all proximal and distal tubular segments, bleb formation and intraluminal casts were observed frequently. Glomerular capillaries were filled with fine precipitates and their endothelium was severely damaged. The results of our studies in the isolated perfused rat kidney (IPRK) model clearly demonstrate a direct dose dependent acute nephrotoxic effect of NaF only for extremely high doses, which, however, may be reached in human cases of severe fluoride intoxication. On the contrary, for low fluoride doses, especially for those concentrations occurring in human plasma upon cariesprophylactic intake of fluorides, no signs of direct acute nephrotoxic action could be observed in the IPRK model.