AbstractSkeletal muscle fibers from dystrophic mice and littermate controls (ReJ‐129) were characterized electrically and then injected with an intracellular marker. In this way they could be identified for examination with an electron microscope to correlate the relative time course of electrical and ultrastructural aherations resulting from the dystrophic process. On the average, dystrophic muscle fibers displayed decreased membrane potentials (−59 ± 1.2vs−79 ± 0.7 mV for normals), decreased specific membrane resistivity (517 ± 27vs642 ± 34 Ω‐cm2for normals), and depressed action potential (AP) maximum rates of rise (+Vmax) (352 ± 9vs417 ± 9 V/s for normals) and amplitudes (92 ± 1.2vs102 ± 1.0 mV for normals) at an experimentally polarized membrane potential of −90 mV. Membrane resistivity and AP +Vmaxwere decreased even in those fibers from dystrophic muscles that displayed normal ultrastructure (classified visually and by ratio of sarcoplasmic reticulum to total cell volume). These findings support the membrane hypothesis of muscular dystrophy that membrane lesions are the primary lesion in t