Beagle dogs were given saline, insulin or the dopamine antagonist, haloperidol, to examine peripheral concentrations of immunoreactive (ir)-pro-opiomelanocortin (POMC) peptides resulting from pars distalis or pars intermedia stimulation. Six beagles were given each test substance on separate occasions with and without dexamethasone pretreatment. Plasma was assayed directly for glucose, ir-ACTH, ir-alpha-MSH, cortisol and, after Sephadex G-50 Fine gel filtration chromatography, for ir-beta-lipotrophin (ir-beta-LPH) and ir-beta-endorphin (ir-beta-END) content. Injection of 0.5 units insulin/kg lowered (P less than 0.01) plasma glucose from 4.9 +/- 0.3 mmol/l (mean +/- S.D., saline controls) to 2.3 +/- 0.5 mmol/l, coincident with increasing ir-ACTH (9.5 +/- 3.1 to 106 +/- 54 pmol/l), cortisol (52 +/- 27 to 221 +/- 27 nmol/l), ir-beta-LPH (not detectable to 34 +/- 18 pmol/l) and ir-beta-END (not detectable to 52 +/- 22 pmol/l). Plasma ir-alpha-MSH concentrations were not affected by insulin. Pretreatment with dexamethasone abolished the ir-ACTH, cortisol, ir-beta-LPH and ir-beta-END increases in response to 0.75 units insulin/kg. Haloperidol (1 mg/kg) increased (P less than 0.01) plasma ir-ACTH (to 103 +/- 63 pmol/l), cortisol (to 243 +/- 11 nmol/l), ir-beta-LPH (to 16 +/- 6 pmol/l), ir-beta-END (to 136 +/- 73 pmol/l) and additionally raised ir-alpha-MSH (7 +/- 8 pmol/l in saline controls to 131 +/- 80 pmol/l after haloperidol).(ABSTRACT TRUNCATED AT 250 WORDS)