The metabolism of guanidino compounds was determined by analysing the incorporation of (15)N from L-(amidino-(15)N)-arginine ((15)N-ARG) into guanidino compounds. (15)N enrichment of guanidino compounds in the plasma, brain, kidney and liver was determined spectroscopically. (15)N-ARG administered intraperitoneally to mice was rapidly distributed to the plasma, kidney and liver, but was highly diluted by ordinary arginine (ARG) in both the plasma and organs. It was found that the rate of uptake of (15)N-ARG into the brain was slower than into the kidney or liver, which suggests that ARG could not pass easily through, or was regulated by the blood-brain barrier. It was also found that (15)N-ARG was metabolized mainly to guanidinoacetic acid (GAA) in the kidney and to urea in the liver. It was further suggested that creatine was synthesized actively in the liver from GAA which was synthesized in the kidney, and then creatine was distributed to the plasma and other organs. The (15)N of (15)N-ARG was incorporated significantly into guanidinosuccinic acid (GSA) and methylguanidine (MG), which indicates that ARG is involved in the synthesis of MG and GSA. MG might be synthesized directly from ARG in the liver, because (15)N in MG was significant 1 min after (15)N-ARG administration. (15)N, however, was not incorporated significantly into guanidinopropionic acid and guanidinobutyric acid.