Functional and specific histamine H2 receptors were characterized in human peripheral monocytes and in U-937 cells, before and after retinoic acid--induced differentiation into monocyte/macrophage-like cells. The relative potencies of histamine and the H1, H2 receptor agonists and antagonists studied are remarkably similar in U-937 cells and U-937 monocytes. There is no change in histamine concentration and activity of the enzymes forming and degrading histamine during monocytic-like differentiation. The results raise the possibility that histamine H2 receptors might be involved in pathophysiological regulations (proliferation/differentiation and biological function) of normal and leukemic monocytes.

Histamine H2 receptor activity (cAMP generation) has been characterized in U‐937 cells before and after retinoic acid‐induced differentiation into monocyte‐/macrophage‐like cells. The differentiation is associated with a decreased capacity of U‐937 monocytes to generate cAMP under basal conditions or after cell surface receptor stimulation by histamine, isoproterenol and PGE1. In contrast, the potencies of the hormones are unchanged during monocytic maturation (EC 50 values = 3.2–4.6 × 10−6 M histamine, 4.6–7 × 10−9 M isoproterenol, 2–4.6 × 10−6 M PGE1). The data support the view that histamine and cAMP‐inducing agents may control the proliferation and differentiation of normal and leukemic cells committed to monocytic maturation in man. They also raise the possibility that normal human monocytes also possess functional H2 receptors and that histamine may be implicated in the regulation of monocyte/macrophage functions.

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