The perichromatin granules were studied in hepatocytes of experimental rats injected with cycloheximide because the increased number of these nuclear components after such treatment facilitated their cytochemical investigation. Most perichromatin granules were sensitive to the digestion with pepsin and ribonuclease. In contrast, small population of perichromatin granules was resistent to such digestion under conditions which remove known RNA containing components such as ribosomes, nucleolar RNP components and interchromatin granules. The size of these resistent perichromatin granules was reduced and they consisted of filaments the width of which was similar to that of filaments in the chromatin. Moreover, a small population of perichromatin granules was sensitive to the digestion with pepsin and deoxyribonuclease. The size of these granules was only slightly reduced. All these observations indicate that most perichromatin granules contain the RNA and some the DNA. A possibility also exists that the perichromatin granules might contain both RNA and DNA but in various proportions. In addition, partial digestion with pepsin followed by a complete digestion with ribonuclease and deoxyribonuclease removed perichromatin granules as well as other nucleoprotein structures. On the other hand, such digestion facilitated the visualization of the nuclear and cytoplasmic skeleton (matrix) in situ.