1. 1. The effects of increasing concentrations of the proteolytic enzyme, trypsin, upon the membranes of the microsomal fraction from rat muscle have been investigated. At low trypsin concentrations, changes in X-ray diffraction characteristics and in the appearance of condensed systems in electron micrographs indicate modification of lipoprotein structure. 2. 2. These changes are closely associated with a loss in ability to accumulate calcium, and are interpreted as being related to a change in lipoprotein structure which produces physiologically leaky vesicles. In this range of trypsin concentrations, morphological breakages in the walls of many of the vesicles are observed and may be related to the changes in lipoprotein structure. 3. 3. Higher concentrations of trypsin produce further modification of the membrane morphology and loss of ATPase activity. © 1969.