The effect in vitro of gastrin-17 and gastrin-34 was studied at concentrations from 10(-12) to 10(-6) M on several functions of resting peritoneal macrophages from BALB/c mice: adherence to substrate, mobility (spontaneous and directed by chemical gradient or chemotaxis), and ingestion of inert particles (latex beads) or cells (Candida albicans). Both gastrins, at concentrations from 10(-10) to 10(-8) M, inhibited significantly all functions studied with the exception of adherence, which was increased. A dose-response relationship was observed, with a maximum inhibition of macrophage functions found at 10(-9) M. These peptides induced in murine macrophages a significant increase of cAMP levels at 60 and 120 s. Adenosine, an adenylate cyclase inhibitor, significantly increased the ingestion of latex beads, whereas the combined presence of adenosine and either G-17 or G-34 produced similar values to those of control samples without adenosine or gastrin. These results suggest that gastrin is a negative modulator of several macrophage functions, and that the inhibition of these activities is carried out through an increase of intracellular cAMP levels.