At least two mechanisms generate tissue differences in the histone subtype composition during development: subtype dilution and subtype replacement. Subtype dilution, which occurs when cells continue dividing after having ceased to synthesize one or more histone subtypes, allows the elimination of stable subtypes. It is the major mechanism generating cell differences in histone composition in sea urchin embryogenesis. Subtype replacement has been observed in mammalian tissues, both in the intact animal and in cultured cells. It is most evident in nondividing cells but occurs to some extent in dividing cells as well. Examples of the two mechanisms are presented and their possible biological significance, as well as that of the differences they produce, is discussed.