In liquid cultures of human cord blood mononuclear cells, the activities of the 2.5S nerve growth factor (NGF) inducing basophil and eosinophil differentiation were investigated. Various concentrations of immunopurified 2.5S NGF derived from murine submaxillary glands were added to cultures with or without conditioned medium from a human T cell line (Mo-CM), which has previously been shown to produce activities stimulating granulocyte-macrophage colonies. Addition of NGF led to significant increases in differentiation of basophilic cells accompanied by histamine synthesis at 2 weeks in vitro; eosinophil differentiation was not increased in these cultures. In addition, NGF could be shown to amplify basophil differentiation induced by Mo-CM, and the activity of NGF inducing basophil differentiation was dependent on the presence of T lymphocytes. These results indicate that NGF stimulates T-lymphocyte-dependent basophilic cell differentiation from human cord blood progenitors and may in this way support differentiation of basophils or mast cells in vivo at sites of allergic tissue inflammation.