Chronic systemic exposure of rats to the neuronotoxic compound trimethyltin (TMT) results in increased incorporation of radioactive precursors into retinal proteins and glycoproteins. Because this increased metabolic activity is accompanied by minimal subcellular pathological alterations and almost no neuronal necrosis, we suggested that it may represent an early, reactive (compensatory) response (Brain Res. 398, 298-304; 1986). We have now investigated the development of this metabolic response to TMT in more detail. Beginning at 30 d of age, rats received weekly doses of TMT (4 mg/kg body wt) by gavage for up to 7 wk; rates of incorporation of [35S]methionine and [3H]fucose into retinal proteins and glycoproteins, respectively, were then determined using in vitro retinal incubations. The apparent rates of protein synthesis and glycoprotein glycosylation in retinas from TMT-treated animals were normal or slightly decreased after 1-3 wkly doses, but were increased after 4 doses and more markedly increased after 7 doses. Glycoprotein glycosylation was increased to a greater degree (192% of control after 7 wk of dosing) than was protein synthesis (134% of control). The increased incorporation in retinas from TMT-treated animals persisted when retinas were incubated with "flooding" concentrations of precursor (1 mM), suggesting that these increases were not owing to alterations in the size of retinal precursor pools. The preferential increase in glycoprotein glycosylation was partially owing to a selective increase in glycosylation of two molecular species with apparent mol wt of 32 and 45 KDa. Quantitative autoradiographic analysis of newly synthesized proteins and glycoproteins indicated that the TMT-induced increase in metabolic activity was not specific or selective for any retinal layer or cell type. We suggest that the preferential activation of glycoprotein glycosylation, and in particular the increased glycosylation of the 32 and 45 KDa glycoprotein species, may represent part of a compensatory metabolic response of retinal neurons to TMT-induced neuronal injury.