The H1 histone is the least conserved of the five major groups of histone proteins. There are as many as five subtypes of H1 histone (1-3). These H1 subtypes occur in different amounts in different animal species and also show tissue specificity (1-3). Normal and neoplastic tissues from the same animal, e.g. rat or calf, contain the same H1 subtypes but in different relative amounts (4, 5). Because H1 subtypes exhibit tissue specificity, it is therefore difficult to identify the changes in their composition that are associated with neoplasia reported in studies utilizing tissues of different origins (4, 5). Tissue culture cells and their in vitro transformed neoplastic counterparts, on the other hand, offer an excellent system in which to study these changes because the cells are derived from the same origin. We have examined normal and neoplastic human cells and found a relationship between the H1 composition and the ability of the cells to form tumors in nude mice. The ratio of H1A to H1B in normal human cells is considerably lower than that in neoplastic cells and this ratio increases with the increased ability of the cells to form tumors in nude mice.