The distribution of transforming growth factor-beta isoforms 1, 2 and 3 and transforming growth factor-beta 2 and 3 mRNAs in adult rat central and peripheral nervous system was examined using Northern blotting and isoform specific antibodies for immunocytochemistry. Transforming growth factor-beta 2 and 3 mRNA were present in all brain areas including cerebral cortex, hippocampus, striatum, cerebellum and brainstem. In sciatic nerve, transforming growth factor-beta 3 mRNA was highly expressed, but transforming growth factor-beta 2 mRNA was not detectable. Transforming growth factor-beta 1-like immunoreactivity was confined to meninges and choroid plexus in the brain and connective tissue in peripheral ganglia and nerves. Transforming growth factor-beta 2 and 3 immunoreactivity entirely overlapped and, in general, were found in large multipolar neurons. Highest densities of immunoreactive neuronal perikarya were present in spinal cord and brainstem motor nuclei, hypothalamus, amygdaloid complex, hippocampus and cerebral cortical layers II, III and V. Most thalamic nuclei, superior colliculi, periaqueductal gray and striatum were almost devoid of transforming growth factor-beta 2- and 3-immunoreactive neurons. Fibrous astrocytes in white matter areas were intensely immunostained. Most dorsal root ganglionic neurons, their satellite cells and Schwann cells in peripheral nerves were also labeled. Transforming growth factor-beta 2- and 3-immunoreactive neurons were localized in brain regions that have been shown to contain neurons synthesizing and/or storing basic fibroblast growth factor suggesting possible opposing or synergistic effects of these peptide growth factors. However, the precise functions of local synthesis and storage of the transforming growth factor-beta isoforms in the nervous system are as yet unknown.