1. The uptake of 3H-(+/-)metaraminol (MA) by tissue slices or pieces was studied in vitro in several peripheral rat organs of varying density of sympathetic innervation (the tissue level of endogenous noradrenaline ranging from 1.7-99.1 nmoles/g). In each individual tissue preparation amine uptake was corrected for entry into the 14C-D-sorbitol space. 2. When the tissues were incubated with 1.4 muM MA, the rate of total amine uptake (i.e., neuronal plus extraneuronal uptake of MA) remained virtually constant for up to 7 min. Therefore, rates of uptake were determined after 2 min of incubation with substrate concentrations ranging from 0.25-12.2 muM. In all tissues the total uptake of MA was saturable. 3. Under the condition of inhibition of neuronal uptake by the presence of 100 muM cocaine, the uptake of MA (considered as extraneuronal amine uptake) was no longer saturable. When tissues were exposed to 1.4 muM MA, the relative contribution by extraneuronal (measured in the presence of cocaine) to total amine uptake (measured in the absence of cocaine) was inversely correlated with the log endogenous noradrenaline content. 4. After correction of the rates of total MA uptake for the cocaine-resistant distribution of the amine, a saturable component of uptake was obtained for each tissue. This uptake was considered to be neuronal; it was subjected to kinetic analysis. 5. Apparent Km values for the neuronal uptake of MA were very similar in all tissues and did not show any dependence on the tissue level of endogenous noradrenaline (average Km = 1.2 muM). 6. V max values for the neuronal uptake of MA were linearly correlated with the endogenous noradrenaline content of the tissues (r = 0.976; P less than 0.001), the V max for the vas deferens being excluded. When related to the content of endogenous noradrenaline, the V max obtained in the vas deferens was lower than that for all other tissues. 7. The results presented here strongly suggest that the membrane site involved in neuronal amine uptake (operationally characterized by the Km of MA) is likely to be identical in all rat tissues and that the number of uptake sites available per nerve terminal does not vary greatly between tissues.