The messenger RNA abundance of proopiomelanocortin (POMC) is increased in neurointermediate lobe (NIL) of rat pituitary when ingesting a high sodium diet (8%; HSD), as is the plasma concentration of the natriuretic peptide γ-melanocyte stimulating hormone (γ-MSH) derived from it. We examined whether the HSD also increases the mRNA abundance in rat NIL of proconvertases 1 and 2 (PC1, PC2), enzymes involved in the processing of POMC into γ-MSH. PC1 mRNA increased by 40% after two weeks of the HSD and by 84% after three weeks. PC2 mRNA increased by 40% after two weeks and by more than 3 fold after three weeks. These results for PC2 were confined to NIL as shown by in situ hybridization at one and two weeks, and were accompanied by a significant increase in NIL PC2 protein after three weeks of the HSD as measured by immunoblotting. The increases in PC1 and PC2 mRNA abundance were paralleled by an increase in POMC mRNA level in NIL. Plasma γ-MSH immunoreactivity averaged 35.1±3.3 fmol/ml in rats on the LSD, but increased to 70.9±4.8 fmol/ml after 3 weeks of the HSD (p < 0.002 vs LSD). These results confirm that the HSD increases the plasma concentration of γ-MSH, consistent with a role for it as a circulating natriuretic peptide. The increased NIL expression of PC1 and PC2 in parallel with POMC in response to the HSD suggests that these changes are part of the coordinated response to states of sodium surfeit.