In order to examine regulation of pituitary intermediate lobe secretion, plasma immunoreactive (i)ACTH, cortisol, and alpha-MSH responses to iv bolus injections of CRF, quipazine maleate (serotonin agonist), isoproterenol (beta-adrenergic agonist) or haloperidol (dopamine antagonist) were determined in conscious, unrestrained dogs. Endocrine responses to these test substances were also determined in dogs pre-treated with dexamethasone. Administration of one or more doses of each test substance resulted in significant elevations in plasma iACTH and cortisol concentrations. Only haloperidol injection caused significant increases in plasma i alpha-MSH. Following dexamethasone pre-treatment, plasma iACTH and cortisol increases in response to all test substances were considerably reduced or abolished. Dexamethasone did not alter baseline or haloperidol-stimulated plasma i alpha-MSH concentrations. However, infusion of bromocriptine mesylate (dopamine agonist) in combination with dexamethasone pre-treatment reduced the plasma i alpha-MSH response to haloperidol. We conclude that a dopaminergic pathway is important in the in vivo regulation of pituitary intermediate lobe activity in dogs.