The uptake of noradrenaline by primary cultures of mouse and rat astrocytes was investigated in order to examine whether an inhibition of extraneuronal noradrenaline uptake was the mechanism whereby some trace biogenic amines potentiate neuronal responses to noradrenaline. In the presence of inhibitors of the enzymes monoamine oxidase and catechol-O-methyl transferase, it was found that astrocytes took up noradrenaline by a temperature-dependent, sodium-independent mechanism that was saturable with a Km = 3.4 x 10(-7) M and a Vmax = 1.6 pmole/mg protein/2 min. This uptake mechanism did not concentrate noradrenaline within the cell. The uptake of noradrenaline was inhibited by ascorbic acid (IC50 = 3.4 x 10(-7) M), adrenaline (IC50 = 7.9 x 10(-7) M), and dopamine (IC50 = 1.5 x 1.0(-6) M). It was not inhibited by the tricyclic antidepressants amitriptyline and desmethylimipramine or the trace biogenic amines beta-phenylethylamine, phenylethanolamine, p- and m-tyramine and p- and m-octopamine. Nor was the uptake inhibited by fluoxetine or 5-hydroxytryptamine. It is concluded that astrocytes take up noradrenaline by a facilitated-diffusion mechanism and that this uptake resembles the extraneuronal uptake described in preparations of brain tissue. It is also concluded that the trace biogenic amines do not potentiate neuronal responses to noradrenaline by inhibiting extraneuronal uptake.