POMC mRNA levels in the intermediate lobe of the pituitary are known to be regulated by osmotic stimuli. Salt loading with 2% saline causes a decrease in POMC mRNA levels in the IL without affecting levels in the anterior lobe. We have investigated possible mediators of this effect and attempted to elucidate the mechanism by which the changes in mRNA levels are brought about. The dopamine D2 receptor antagonist domperidone blocked the inhibitory effect of salt load on POMC mRNA in the neurointermediate lobe, while the D2 agonist bromocriptine mimicked the effect of salt load. Pharmacological agents affecting D1 receptors, beta-adrenoceptors, and endogenous serotonin levels did not block the decrease in POMC mRNA levels after a salt load. The level of transcription of the POMC gene in the neurointermediate lobe was investigated using a nuclear run-on transcription assay. Transcription of POMC was found to be unchanged after a salt load, indicating that an osmotic stimulus does not decrease POMC mRNA levels by a specific change in the level of transcription.