We investigated whether astrocytes store and synthesize agmatine (decarboxylated arginine), an endogenous ligand for imidazoline and alpha 2-adrenergic receptors, in brain. Agmatine, detected chemically and immunocytochemically, is contained in cultured astrocytes and C6 glioma cells (8.5 +/- 1.4 and 1.8 +/- 0.6 nmol mg-1 protein, respectively). Glial membranes express activity for arginine decarboxylase (ADC), the biosynthetic enzyme for agmatine (astrocytes 85.4 +/- 9.2; C6 cells 18.2 +/- 3.12 nmol h-1 mg-1 protein). Lipopolysaccharide, and inducer of glial nitric oxide synthase (iNOS), significantly reduced (C6) or did not affect (astrocytes) ADC activity. Inferferon-gamma, not affecting iNOS, elevated ADC activity in both cell types. Astrocytes are a site of synthesis and storage of agmatine. ADC and iNOS enzymes synthesizing distinct bioactive products from L-arginine, may be reciprocally regulated.