Abstract The release of histamine by normal human leukocytes (basophils) following in vitro challenge with activated complement (zymosan-treated serum) was previously reported. In this study, the effects of various pharmacologic agents on this release mechanism were compared with allergen-induced release of histamine. Colchicine and vinblastine antagonize the polymerization of tubulin to form microtubules, and both agents inhibited complement- and allergen-mediated release of histamine. The dose-response effects of these drugs were quite similar for the two release mechanisms. Deuterium oxide, an agent which stabilizes microtubules, enhanced both complement- and allergen-triggered release of histamine from basophils. Finally, treatment with cytochalasin B, a fungal product known to interfere with microfilament formation, resulted in enhanced release of histamine from complement-treated basophils but no significant change in the percentage of histamine released from allergen-treated basophils. These findings suggest that microtubules and/or microfilaments are involved in complement-induced secretion of histamine by human basophils.