The present study assessed 5-HT3 receptor recognition site levels in homogenates of putamen derived from patients with clinically and neurochemically diagnosed Huntington's disease or Parkinson's disease and those from age-, sex- and post-mortem delay-matched neurologically and psychiatrically normal patients to investigate the cellular location of 5-HT3 receptors in the human putamen. Specific [3H]granisetron (0.91 nM) binding (defined by ondansetron, 10 microM) was significantly reduced in putamen homogenates from eight out of ten patients with Huntington's disease compared to similar homogenates from 'control' patients (72 +/- 6 and 39 +/- 8 fmol/g wet weight, mean +/- S.E.M., n = 10 and 8, tissue from 'control' and Huntington's disease patients, respectively, P = 0.004). In contrast, specific [3H]granisetron (1.04 nM) binding levels were similar in putamen homogenates from patients with Parkinson's disease when compared to homogenates from 'control' patients. The present results indicate that at least a proportion of the 5-HT3 receptor population in the human putamen is located on neurones that have their cell bodies within this brain region and that these receptors are not primarily located on dopamine neurone terminals in the human putamen.