Intrastriatal injections of excitotoxic amino acids and their analogues (for example kainate and ibotenate) elicit a pattern of neuronal degeneration that is similar in many respects to that observed in Huntington's disease. In this disease there is a progressive degeneration of most types of intrinsic neuron but somatostatin and neuropeptide Y levels are increased 3-5-fold. This may be attributed to the selective preservation of a sub-class of striatal aspiny neurons, in which these two peptides are co-localized together with the enzyme NADPH-diaphorase. Beal et al. reported recently that following intrastriatal injections of quinolinic acid in rats, medium-sized aspiny neurons were selectively preserved and they suggested that quinolinic acid which is found in human brain might cause the neuronal degeneration seen in Huntington's disease. We have used immunocytochemical and enzyme histochemical techniques to examine this selective toxicity but find no evidence to support this finding. We conclude that there are substantial differences between the immunocytochemical changes detected in postmortem Huntington's disease brain and those following quinolinic-acid-induced degeneration.