Power line interference is a major problem in high-resolution biopotential measurements. Because interference coupling is mostly capacitive, shielding electrode leads and a high common-mode rejection ratio (CMRR) are quite effective in reducing power-line interference but do not completely eliminate it. We propose a model that includes both interference external to the measuring system and interference coming from its internal power supply. Moreover, the model considers interference directly coupled to the measuring electrodes, because, as opposed to connecting leads, electrodes are not usually shielded. Experimental results confirm that reducing interference coupled through electrodes yields a negligible interference. The proposed model can be applied to other differential measurement systems, particulary those involving electrodes or sensors placed far apart.