We have already reported that renal glycine amidinotransferase (GAT) activity decreases in the course of renal damage, however, the inability of the kidney to synthesize guanidinoacetic acid (GAA) may be compensated by the pancreas in a more advanced stage of renal failure, and that in diabetes mellitus, the production of GAA is decreased from the period without renal dysfunction, and the extrarenal production of GAA is also decreased. In order to elucidate the significance of GAA synthesis in the pancreas, the author measured serum concentration of GAA, creatine, and the renal and pancreatic GAT activity in control, streptozotocin (STZ)-induced diabetic, insulin-treated diabetic, and ethionine-induced acute pancreatitis rats. The serum GAA concentration was depressed in untreated diabetic rats (21.5 +/- 2.5 micrograms/dl) compared with the level in controls (85.5 +/- 10.1 micrograms/dl), and was restored to control level by insulin treatment (66.2 +/- 7.3 micrograms/dl). The renal and pancreatic GAT activities were depressed in untreated diabetic rats compared with the level in controls and the latter was restored (625.2 +/- 96.2 micrograms/g.tissue/h) by insulin treatment. The positive correlation was observed between pancreatic GAT activity and serum GAA concentration. The serum GAA concentration was significantly higher in acute pancreatitis rats (716.0 +/- 223.7 micrograms/dl) compared with the level in controls, although the renal and pancreatic GAT activities were lower in acute pancreatitis rats compared with the level in controls. These results indicate that in STZ-induced diabetic rats, depressed pancreatic GAT activity was ameliorated by insulin treatment, consequently the level of serum GAA was restored and that GAA might be released from the acinar pancreas, resulting in higher concentration of serum GAA in acute pancreatitis rats. GAA may be synthesized in the acinar pancreas, and insulin can directly regulate the function of acinar pancreas including GAA synthesis.