At present it is not clear whether N-methyl-D-aspartate and N-methyl-D-aspartate receptor agonists have a direct excitotoxic effect on somatostatin interneurons in rat striatum. The N-methyl-D-aspartate receptor comprises a multivariant complex encoded by a family of subunit complementary DNAs. Evidence suggests that expression of the N-methyl-D-aspartate receptor subunit NR1 (zeta 1) is essential for functional receptors. To investigate the expression of NR1 messenger RNA by striatal somatostatin cells, a dual in situ hybridization technique was applied to fresh frozen tissue sections. Cellular sites of NR1 and somatostatin gene expression were visualized in the same tissue section using [35S]NR1 and alkaline phosphatase-labelled somatostatin oligonucleotides. Only 8-18% of striatal somatostatin cells expressed a strong NR1 hybridization signal; most cells (> 80%) expressed a weak or undetectable signal. In contrast NR1 messenger RNA was enriched in neighbouring medium-sized non-somatostatin cells. These data suggest that while the NR1 gene is expressed in some striatal somatostatin cells most do not express a strong NR1 signal, a finding which may explain, in part, the preferential survival of somatostatin cells in Huntington's disease.