Noradrenergic reuptake blockade is a recognised mechanism of antidepressant action, but the extent of the blockade necessary for therapeutic effect is not known and plasma levels do not provide a guide to therapy. We report a method to assess noradrenaline reuptake blockade in vivo in man using [11C]meta-hydroxyephedrine and the multiple organs' coincidences counter. Eight healthy volunteers had two scans, one with tracer alone and one after preloading with desipramine 50-75 mg p.o. In all subjects, there was an increased washout rate of the radioligand from the heart following preloading (t=4.38; P<0.003) as well as a decrease of the area under the [11C]meta-hydroxyephedrine time activity curve (t=7. 4; P=0.001). In one subject who had three doses of desipramine, the increase in washout rate was dose-dependent. In conclusion, [11C]meta-hydroxyephedrine in the multiple organs' coincidences counter gives a valid, low radiation method to assess noradrenergic reuptake blockade in the clinic.