[3H]Nisoxetine ([3H]NIS) was used to measure uptake sites for norepinephrine (NE) in the locus coeruleus (LC) of humans. Regression analysis demonstrated an inverse correlation between age and the binding of [3H]NIS to NE uptake sites in the LC (r = −0.6; P<0.01). Since considerable cell loss has been reported to occur with age in the human LC, the decreased binding of [3H]NIS probably reflects loss of LC cells rather than a down-regulation of these sites.