The levels and distribution between nucleus and cytoplasm of HMG1 and HMG2 proteins have been investigated in different tissues of mammals. In lymphoid tissues and testis high amounts of these proteins are present in both nuclei and cytoplasm, while in the hepatic tissues and brain they accumulate in cytoplasm, mainly in the cytosol. In particular, very low amounts, if any, of HMG1 and 2 are present in the nuclei active for DNA replication (rat regenerating liver and primary hepatoma) or transcription (adult liver and brain). Therefore, it appears that HMG1 and 2 are not necessary for these processes. On the other hand, nuclear (chromosomal) HMG1 and 2 are characteristic for the tissues containing undifferentiated cells: lymphoid tissues, testis, neonatal liver. These proteins are bound to the chromatin regions solubilized early by sonication or DNase action. Comparison of the data obtained for different tissues shows an inverse correlation between the amounts of chromosomal HMG1 and 2, on the one hand, and of histone H1°, on the other hand. These results suggest that chromosomal HMG1 and 2 take part in the processes that occur during cell differentiation, while histone H1° is induced to preserve differentiated cells from dedifferentiation.