A large number of genetically modified mice are now available that can be used to elucidate the role of the deleted, mutated, or over-expressed genes for regulation of physiological functions. The impact of anaesthesia on physiological parameters in the mouse is such that it could overshadow subtle changes induced by gene manipulation. Therefore, many approaches have been attempted to measure physiological parameters in conscious mice (Janssen and Smits, 2002). A major control mechanism is the sympathetic nervous system, yet there have been few reports of its successful measurement in the conscious mouse. In the present study, we report a method to reliably measure renal sympathetic nerve activity in freely moving mice. C57BL/6J mice (n=4), weighing over ~ 25g, were used for all experiments. Procedures were undertaken in accordance with National guidelines. Mice were anaesthetized with pentobarbital sodium (45 mg Kg^-1 I.P.). Electrodes were implanted for the measurement of renal sympathetic nerve activity (RSNA), using an adaption of the method employed in rats (Miki et al. 2002). Briefly, the left kidney was exposed retroperitoneally. The sympathetic nerves running alongside the renal artery or vein were carefully dissected free of connective tissue. A piece of laboratory film (~1 mm x 2 mm) was placed under the dissected nerve. The two tips of the electrodes were hooked onto the nerve by placing the electrodes between the renal nerve and the sheet. The exposed nerve and the electrode were embedded in a two-component silicone gel (932, Wacher-Chemie, Munich, Germany). Subsequently, the electrode for the measurement of the electrocardiogram (ECG) was also implanted. After 2 days of recovery, recordings were carried out in a sound attenuated, temperature (24°C) controlled chamber. Animals were killed with an anaesthetic overdose. Data (means ± S.E.M.) were subjected to the Fisher’s least significant difference test and significance taken as P<0.05. The renal sympathetic nerve activity was recorded successfully without contamination by external noise such as that from the electrocardiogram and/or electromyogram. The renal sympathetic nerve activity was increased to 299 ± 12 % (P<0.05) during movement from 100% of the non-REM and quiet awake state and heart rate was concomitantly increased from 576 ± 3 beats min^-1 of the non-REM sleep and quiet awake level to 706 ± 3 beats min^-1 (P<0.05). Successful recordings could be made for up to 5 days. This novel method for measurement of the RSNA could be usefully employed in studies on the role of sympathetic nerve activity in regulating physiological function in genetically modified mice.