The effects of exogenously (NH4Cl ingestion) and endogenously (streptozotocin-diabetes) generated chronic metabolic acidosis on the abundance of rat renal mRNAs have been examined. 2. Total RNA was translated in vitro and the translation products analyzed by two-dimensional gel electrophoresis. 3. The translation product identified as phosphoenolpyruvate carboxykinase (PEPCK) increased 3.5-fold in both acidosis and diabetes. 4. This increase was not observed in diabetic rats treated with NaHCO3. 5. The abundance of one other translation product increased in acidosis. 6. That of 10 others increased in diabetes, several of which were elevated regardless of acid-base status. 7. The abundance of one translation product decreased in acidosis and diabetes but not in NaHCo3 treated diabetic rats, indicating acid-base regulation of this product. 8. The results establish that the acidosis response is limited to a small number of renal mRNAs and confirm that renal PEPCK is primarily regulated by changes in acid-base status. 9. They also indicate that diabetes affects the abundance of specific renal mRNAs through mechanisms independent of acid-base status.