Bombesin (BBS) was infused in conscious fasting dogs to document its effects on the release of motilin in the blood and on intestinal motility. When BBS was infused for 3 h (0.125 and 0.5 microgram X kg-1 X h-1), a specific pattern of myoelectric activity was induced: 1) the pacesetter potentials were increased in frequency but decreased in amplitude; 2) a moderate spike activity (weak phase II) was superimposed on this disorganized pacesetter activity, and activity fronts were abolished despite elevated motilin levels. A second experiment was performed in which motilin levels during BBS administration for a selected period of an interdigestive myoelectric complex (IDMC) could be compared with those obtained at a similar period of a preceding IDMC in which a saline solution had been infused. The motilin blood levels measured during BBS administration (0.25, 0.5, 1.0, and 2.0 micrograms X kg-1 X h-1 for 20 min each stepwise) were significantly higher than those obtained with saline. The administration of BBS synchronized with the IDMC was necessary to document its effect on motilin release, because when BBS was infused at an unknown period of the IDMC no rise of motilin levels over basal could be detected. Because of its contradictory effects on the release of motilin (stimulation of motilin release) and on the IDMC (inhibition of motilin effect), a physiological role of BBS as an endocrine regulator of motilin release is questionable. On the other hand, the possibility that BBS controls motilin release in a paracrine or neurocrine role cannot be excluded.