The purpose of the present study was to examine the effects of microtubular-microfilament (MT-MF) modifying agents on gastrin release from antral mucosal cells maintained for 3 days under tissue culture conditions. Gastrin levels in the media, determined by radioimmunoassay, were monitored at hourly intervals for 6-8-hr periods. Colchicine, 1 mM, produced mild depression in media gastrin levels and completely inhibited dcAMP-theophylline-induced gastrin release. Ethyl alcohol depressed secretion of gastrin. Conversely, colchicine at 0.01 mM, significantly increased levels of gastrin. Gastrin levels were also significantly increased by tetracaine, 1 mM, and by deuterium oxide, 75% and 37.5%. Cytochalasin D had little effect on resting gastrin levels. Results of these experiments indicate response of gastrin-producing cells maintained under these conditions to a number of test agents; that the secretory responses of gastrin cells to the MT-MF modifying agents are similar to those of other endocrine cells in which concommitant changes in the MT-MF system have been studied, providing support for the proposal that this system is involved in the sequence of intracellular events which leads to gastrin secretion.