A unique voltage clamp circuit for certain biological investigations, which features the provision of maintainingthe clamped region at ground potential with the residual error balanced about ground, is discussed. Theoreticalconsideration of the circuit function indicates that the possibility of error arising from stray current pathways andloading of the electrodes is reduced by holding the clamped region close to ground. An additional secondary feedbackloop, in conjunction with this circuit, reduces switching transients and other high frequency noise and allowsdynamic balance of the clamped region about ground potential despite assymmetries in the experimental circuit.This circuit has been employed, using commercially available operational amplifier units, to clamp the isolatedfrog skin for measurement of sodium transport flux. In this application, the assembly clamped the skin to wellwithin 1 mv, with excellent dc stability and a theoretical error of 0.1% in response to 1-msec transients.