Human basophils in contact allergy empty granules slowly--a secretory process termed piecemeal degranulation in contrast to the explosive extrusion of granules seen in anaphylactic degranulation. An ultrastructural enzyme-affinity method to detect histamine, employing diamine oxidase coupled to gold, was used to localize this proinflammatory mediator in human basophils stimulated to release histamine by FMLP. Cytoplasmic vesicles and granules of human basophils so stimulated for 20 s were gold-labeled, indicating the presence of histamine. Cytoplasmic vesicles may play a key role in the secretion of histamine from basophils in those diseases characterized by the ultrastructural morphology of piecemeal degranulation.