Application of differential scanning calorimetry to nuclei from rapidly growing mouse neuroblastoma cells showed a melting profile with four major thermal transitions: I (60 degrees C), II (76 degrees C), III (88 degrees C), and IV (105 degrees C). When neuroblastoma cells were induced to differentiate by serum withdrawal or treatment with sodium butyrate, transition IV disappeared, while transition III increased in magnitude. Comparison was made to nuclei from several types of nondividing cells as well as a number of samples from mature tissues. In rapidly dividing cells the predominant endotherm was IV (105 degrees C), while in nondividing cells, transition III (88 degrees C) predominated the calorimetric profile. Cellular differentiation thus appeared to be accompanied by a major change in chromatin structure, as evidenced by a shift in melting temperature from 105 to 90 degrees C, and this may serve to distinguish the Go phase of the cell cycle from G1.