Despite extensive biochemical and morphological studied on the degenerative muscle diseases, the primary chemical lesions are still obscure, both in humans and animals. In this report we examine the activities of the lysosomal endoproteinase cathepsin B and its endogenous inhibitor(s) in the red and white skeletal muscles of guinea pigs with nutritional muscular myopathy induced by vitamin E deficiency. We observed a twofold increase (P less than 0.005) in the activity of cathepsin B in the white skeletal muscles of the vitamin E-deficient (E-) animals over that of the normal (N) and control (E+) groups. Assessment of the activity of endogenous cathepsin B inhibitor revealed a one and a half times greater amount of inhibitor in N when compared to E-; this difference in inhibitor activity applied to both red (masseter) and white (medial head, gastrocnemius) muscle. When the specific activity of cathepsin B in the E-tissue was corrected for inhibitor activity, the corrected value was not significantly different from either the E+ or the N tissue.