Regional distribution of gene expression of the axonal growth-associated protein, GAP-43, was studied in adult rat brains by in situ hybridization autoradiography to determine the features of mature neuronal populations that synthesize GAP-43 protein. Such synthesis appears to correlate with axonal growth during maturation and regrowth after axotomy. In most adult neurons, the sharp decline in GAP-43 gene expression implies a reduced capacity for axonal growth. Neurons capable of extending axonal knobs in the absence of injury may indicate a "plasticity" underlying dynamic processes of interaction between neurons and their synaptic targets. Antisense and sense (control) riboprobes were used on serial sections in the three principal axes, and the magnitude of hybridization signal was examined to determine regional patterns. GAP-43 mRNA levels are pronounced in diverse neuronal groups including the locus coeruleus, raphé nn., dopaminergic nigral and ventral tegmental nn., mitral cells, hippocampal CA3, inferior olivary n., vagal motor n. and other parasympathetic preganglionic neurons, select thalamic midline and intralaminar nn., several specific nn. of the hypothalamus and basal forebrain, the granular layer of cerebellar cortex, the infragranular neocortex, and the granular olfactory paleocortex; there is a substantial range in the magnitude of expression. Regions revealing minimal signal include most thalamic sensory relay nuclei, the granule neurons of the olfactory bulb and dentate gyrus, and the caudate and putamen. Possible concomitants of GAP-43 expression include regulation of ion flux and neurotransmitter release. Those neurons with long, extensively dispersed and numerous synaptic connections display the strongest signals and may possess the greatest propensity for continuous growth and turnover of their axon terminals, in contrast to short-axon and specific projection neurons exhibiting minimal levels. These data may enable inferring which populations display normal or experimentally induced axonal growth.