In liver, kidney, and lung of the mouse, two of the major H1 subtypes present at 1 week after birth, H1a and H1b, decline to nearly undetectable levels by 8-16 weeks, and a third subtype, H1d, also diminishes. The amounts of two other H1 subtypes, H1e and H1 degrees, increase markedly and that of another, H1c, also increases. The disappearance of H1a is almost complete by the age of 4 weeks, whereas the decline in H1b occurs largely between 4 and 16 weeks, when most cells are nondividing. A decline in H1a was observed also in cultured mouse embryo fibroblasts after they became quiescent. Furthermore, in the quiescent fibroblasts, the synthesis of H1a and H1b was preferentially reduced. In the thymus, newly formed nondividing cells have as much H1a and H1b as the dividing cells from which they are derived, but circulating lymphocytes have less H1a and H1b and more H1e, indicating that molecules of H1a and H1b are removed from chromatin, and H1e deposited, after cell division ceases. H1 degrees, however, is not present in thymocytes or peripheral blood lymphocytes. Our results indicate that 1) there are no tissue-specific H1 subtypes among the somatic tissues examined; 2) H1a and H1b are synthesized in large amounts only in dividing cells, whereas H1c, H1d, and H1e are synthesized in both dividing and nondividing cells; 3) different H1 subtypes are degraded at different rates in nondividing cells; and 4) H1e always, and H1 degrees sometimes, accumulates in nondividing somatic cells. We conclude that alterations of the H1 composition of chromatin are a general feature of nondividing cell formation; that such alterations are made, in large part, after the nondividing cells are formed and are accomplished both by changes in the pattern of synthesis of the various H1 subtypes and by differential loss of subtypes; and that each H1 subtype differs from the others in some or all of the properties that we have examined, supporting the idea that the individual H1 subtypes differ from each other in some of their functions.