The aim of this study was to test whether cholinergic mechanisms regulate dopamine (DA) release from the carotid body (CB) and interact with DA D(2) autoreceptors. One hundred forty-two CBs from adult rabbits were infused in vitro in a surviving medium bubbled with O(2) (Bairam A, Marchal F, Cottet-Emard JM, Basson H, Pequignot JM, Hascoet JM, and Lahiri S. J Appl Physiol 80: 20-24, 1996). CB DA content and release were measured after 1 h of exposure to various treatments: control, cholinergic agonist (0.1-50 microM carbachol), full muscarinic antagonist (1 and 10 microM atropine), antagonists of M(1) and M(2) muscarinic receptors (1 and 10 microM pirenzepine and 10 microM AFDX-116, respectively), and the DA D(2) receptor antagonist domperidone (1 microM), alone and with carbachol (1 microM). Compared with control, the release of DA was significantly increased by carbachol (1-50 microM), AFDX-116, and domperidone and decreased by atropine (10 microM) and pirenzepine (10 microM). The effects of domperidone and carbachol were not significantly different but were clearly additive. It is concluded that, in the rabbit CB, M(1) and M(2) muscarinic receptor subtypes may be involved in the control of DA release, in addition to the DA D(2) autoreceptors.