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The authors report on (1) the absorption of agmatine from the gastrointestinal tract as an important source of this polycation in the organism, (2) its organ distribution, and (3) its putative role in liver regeneration. When rats received 0.5 microCi [(14)C]agmatine contained in 5 grams of standard rat chow after a fasting period of 24 hours, radioactivity was recovered in all organs investigated, in blood, and in urine. In the liver 67% +/- 7% of administered radioactivity was found. After partial (two-thirds) hepatectomy, administration of 250 mg and 500 mg agmatine by gavage for 6 days reduced liver regeneration at day 7 by 20% and 22%, respectively, compared with animals that received no agmatine. Agmatine is absorbed from the gastrointestinal tract, probably by means of a specific transporter. It is likely that agmatine in the chyme of the gut represents an essential source of agmatine in the tissues of the organism. An increase in the availability of gastrointestinal agmatine for absorption impairs liver regeneration and may contribute to the development of liver diseases.