An ultrastructural analysis of human basophils stimulated with anti-IgE, recombinant histamine-releasing factor (rHRF), or monocyte chemotactic protein-1 (MCP-1) (compared with unstimulated cells) was performed. Partially purified peripheral blood basophils were prepared for electron microscopy at time points known to precede histamine release and at half-maximum histamine release times for each secretagogue. Activation morphologies associated with stimulation included granule-vesicle attachments, piecemeal degranulation, anaphylactic degranulation, and uropod formation. These features were qualitatively similar in the stimulated samples. Quantitative differences were evident, however, when stimulated samples were compared with controls or at different time points after stimulation with a single agent or when individual secretagogues were compared. All stimulated samples differed quantitatively from the control samples. Rank orders for morphologic activation events revealed that the most effective trigger for anaphylactic degranulation was anti-IgE > MCP-1 > rHRF, whereas the most effective trigger for uropod formation was rHRF > anti-IgE > MCP-1. Rank orders for piecemeal degranulation and granule-vesicle attachments were the same: MCP-1 > anti-IgE > rHRF. Important relationships among these anatomic events reveal that the development of motile configurations is not associated with the development of secretion morphologies and that piecemeal degranulation precedes and is inversely related to anaphylactic degranulation in stimulated samples. (J ALLERGY CLIN IMMUNOL 1996;98:355-70.)