The effect of trypsin on the morphology of the rat liver microsomal fraction isolated by differential centrifugation has been investigated. The microsomes were incubated at 37°C and centrifuged thereafter under the conditions of their initial isolation. The trypsin-treated microsomes and the untreated controls were fixed in unbuffered osmium tetroxide and embedded first in gelose and then in methacrylate. In the trypsin-treated microsomes, there was a removal of the ribosomes from the rough vesicles. Parallel chemical determinations showed that the total nitrogen and total phosphorus of the pellet were lowered. Particles, densely stained with phosphotungstic acid (PTA) and homogeneous in appearance, were found within microsome smooth vesicles in a fluffy layer which collects on the top of the microsome pellet. The morphology of these PTA-stained particles remained unchanged after incubation with trypsin.