Assays of neuron-localized (neurotypic) and glia-localized (gliotypic) proteins were used to detect and characterize the toxic effects of tributyltin (TBT) on the developing CNS. Four proteins associated with specific aspects of neuronal and glial development were evaluated: (1) p38, a synaptic vesicle-associated protein; (2) neurofilament 200, an intermediate filament protein of the neuronal cytoskeleton; (3) myelin basic protein, an oligodendroglia and myelin-sheath associated protein; and (4) glial fibrillary acidic protein, an intermediate filament protein of astrocytes. The amount of each protein in homogenates of cerebellum, forebrain and hippocampus was determined by radioimmunoassay. A single administration of TBT (2, 3, or 4 mg/kg, i.p.) on postnatal day 5 caused dose- and region-dependent decreases in brain weight with the cerebellum being most affected. These decrements were not associated with light microscopic evidence of altered brain development but were accompanied by large dose- and region-dependent decreases in p38 and myelin basic protein. Decrements in both the per tissue (total) and per milligram of tissue protein (concentration) values for these proteins were observed in cerebellum and forebrain; hippocampus was largely unaffected. (Copyright (c) 1988 The Journal of Pharmacology and Experimental Therapeutics.)