In addition to its known effect on renal tubular transport, frusemide (furosemide) has been shown to affect renal circulation. This study in the anaesthetised rat examined the influence of frusemide (bolus 0.25 or 0.5 mg kg-1 I.V., then infusion delivering the same dose over 1 h) on renal cortical and medullary circulation measured as laser-Doppler blood (cell) flux. The responses were compared with simultaneously measured changes in renal excretion and in the tissue admittance, an index of medullary ionic hypertonicity of the interstitium. Renal vascular responses to frusemide were significant but not dose dependent. During low-dose frusemide infusion cortical flux decreased 11.5 ± 0.9 % and medullary flux decreased 32.3 ± 3.5 % (difference significant at P < 0.001). During high-dose infusion the decreases were by 13.5 ± 1.4 and 29.3 ± 3.8 %, respectively (difference significant at P < 0.001). Sodium excretion increased 15-fold (by 3.7 ± 0.4 µmol min-1) and 30-fold (by 5.9 ± 1.1 µmol min-1) during low- and high-rate infusion of frusemide, respectively. By contrast, medullary tissue admittance decreased similarly with the two doses: maximally by 13.4 ± 1.4 and 10.9 ± 0.9 %, respectively. The observations that an exaggerated post-frusemide decrease in blood flow within the medulla coincided with decreasing tissue admittance in this zone and that neither medullary blood flow nor admittance changes were related to the dose suggest a causal relationship between interstitial ionic hypertonicity and vascular resistance. We propose that the post-frusemide decrease in medullary tissue NaCl depressed medullary circulation by inhibiting local generation of vasodilator prostaglandins.