The present study demonstrates that large aspiny neurons, containing the enzyme acetylcholinesterase (AChE), are relatively preserved in the caudate nucleus and putamen in Huntington's disease (HD). Although histochemical evidence indicates that AChE and choline acetyltransferase (ChAT) co-localize within the same striatal neurons, measurements of ChAT activity showed significant reductions in enzyme activity, as others have reported. Reduced ChAT activity in the presence of presence of persistent AChE-positive neurons may be a consequence of loss of synaptic terminals resulting from the death of spiny neurons. The selectivity of neuronal sparing in HD may be related to the patterns of synaptic contact or a paucity of excitatory amino acid receptors on striatal aspiny neurons.