A quantitative pharmacohistochemical technique has been used in the present study to assay acetylcholinesterase (AChE) activity in the neostriatum of C57BL/6 and DBA/2 mice. This technique permits the measurement of enzyme activity into microscopically defined compartments and is suitable for the study of striatal AChE-containing, putatively cholinergic, neurons. Microphotometric measurements have been performed in the cytoplasm of AChE-containing perikarya and in the striatal matrix: in both compartments, AChE activity was significantly higher in DBA/2 than in C57BL/6 mice. The present data show that AChE quantitative pharmacohistochemistry is suitable for studying the enzyme activity in nervous tissue and, particularly, in the cytoplasm of individual AChE-containing neurons. In addition, interstrain comparison indicates the presence of a genetically determined higher AChE content in striatal neurons of the DBA/2 strain.