The different responses of neurons with distinctive variations in morphology and function, confirm earlier observations of the lack of uniformity in the reaction of nerve cells to trimethyltin. Thus, hippocampal pyramidal and cortical neurons in both rat and Mongolian gerbil (M. unguiculatus) show abundant lysosomal dense bodies and disorganisation of the protein-synthesising apparatus. Cerebellar Purkinje cells in gerbil, but not in rat, show striking increases in smooth membrane systems, while dense bodies are insignificant in both species; large motor-type neurons in brain stem and spinal cord in both species do not accumulate dense bodies, but their rough endoplasmic reticulum (RER) may undergo intense vacuolation with or without subsequent cell death; and by contrast, spinal ganglion cells of both species may form an excess of dense bodies and, in the gerbil, vacuolation of RER. In contrast with these varied responses to trimethyltin most neurons, large and small, in both species regularly undergo striking vacuolation of the Golgi apparatus in the earliest phase of the intoxication, a constant feature that probably reflects the site of the primary cytotoxic lesion; all other changes we consider are secondary to such damage to the Golgi apparatus, however this may come about. These observations are discussed in relation to earlier reports of the variable effects of trimethyltin and with the metabolic changes reported in trimethyltin intoxication that in general accord with these morphological conclusions.