The authors are characterizing toxicant-induced injury to the nervous system by measuring nervous system cell-type specific proteins together with accompanying changes in morphology and behavior. In the present study, cerebellar neurotoxicity was assessed in the Gunn rat an autosomal recessive mutant that exhibits degeneration of Purkinje cells due to hereditary hyperbilirubinemia. Five proteins associated with neuronal or glial cell types were chosen for evaluation as follows: (1) G-substrate, a Purkinje cell-specific phosphoprotein that serves as the endogenous substrate of cyclic GMP-dependent protein kinase; (2) PCPP-260, a Purkinje cell-specific phosphoprotein that serves as an endogenous substrate of cyclic AMP-dependent protein kinase; (3) synapsin I, a synapse-specific phosphoprotein present in all neurons; (4) glial fibrillary acidic protein, an astrocyte-specific protein; and (5) myelin basic protein, a protein unique to myelin.