The phosphorylation of H1 histones is reviewed. Consideration is given to phosphorylation reactions which occur in both replicating and nonreplicating cells. The available evidence suggests that H1 histones accept phosphate groups at different sites in response to different stimuli. The tentative location of the acceptor sites is summarized, and the effects of site-specific phosphorylation on the conformation of H1 histones in vitro is discussed. The phosphorylation of H1 histones which occurs during cell replication is reviewed in detail, and it is concluded that there is no clocklike mechanism which couples the phosphorylation of a particular site or region in H1 histones to a set point in the cell cycle. There is both species-and cell-specific variability in the phosphorylation of H1 histones during cell replication. Recent studies are discussed which show that an interspecific somatic cell hybrid of mouse and Chinese hamster can replicate the Chinese hamster genome in a stable manner using only mouse H1 histones and their phosphorylated forms. I speculate that H1 histone phosphorylation is a mechanism for the relaxation of long-term structures needed for differential gene activity in order to attain the short-term goal of genome replication.