Protein metabolism was studied in the regenerating rat pancreas acinar cell by (3)H-leucine autoradiography. Rats were placed for 10 days on a protein-free ethionine (PFE) regimen which caused necrosis of most of the acinar cells. Withdrawing the PFE regimen and instituting a stock diet (SD) on day 11 was followed by good restitution of acinar cell morphology. DNA synthesis peaked at day 15. Intraperitoneal injection of (3)H-leucine and sacrifice at 5, 10 and 30 minutes and at 1, 4 and 24 hours after injection at PFE-SD days 10, 12, 15 and 29 and at the same time periods in control SD animals provided tissue for autoradiography. At PFE-SD days 10, 12 and 15, there were great increases in the concentration of autoradiographic grains over the nucleolus, nucleus and cytoplasm of acinar cells as compared to similar compartments in SD animals. There also were more total grains per nucleus and nucleolus in the PFE-SD animals at these days. The grains per unit area of nucleus and cytoplasm of PFE-SD acinar cells at days 10, 12 and 15 increased to about the same degree, but the increase in concentration of grains per unit area of nucleolus was much higher than in the two other compartments. The increase in total number of grains in the nucleolus was much higher than that per nucleus in PFE-SD animals on days 12 and 15. Some of the disproportionately high concentration and amount of newly synthesized labeled protein in the nucleolus at PFE-SD days 12 and 15 may have been involved in genomic activity, giving rise to the peak of DNA synthesis at day 15.