The effect of Sr++, Ba++ and Mn++ on calcium uptake by a plasma membrane-enriched fraction from mesenteric arteries of spontaneously hypertensive rats (SHR) was studied to determine what alterations in divalent cation interactions are associated with hypertension. <sup>45</sup>Ca++ uptake in the presence of ATP by this fraction from SHR was significantly greater than that of normotensive rats (NWR). This <sup>45</sup>Ca++ uptake by these fractions from both types of rat could be reduced by Ba++, Sr++ and nonradioactive Ca++, but not by Mn++; the ability of these cations to compete with <sup>45</sup>Ca++ was in the following order Ca++ > Sr++ > Ba++. In contrast, <sup>45</sup>Ca++ uptake in the absence of ATP by this subcellular fraction from SHR was significantly less than that of NWR, and this passive <sup>45</sup>Ca++ binding could be displaced by Mn++ in addition to the other cations. Both qualitative and quantitative differences were found between SHR and NWR in this study of the effects of cations on calcium uptake by arterial plasma membrane. These results suggest that 1 This investigation was supported by the Alberta Heart Foundation and the Medical Research Council of Canada. 2 In this paper, calcium uptake is used operationally to describe all processes (binding, transport, etc.) leading to calcium accumulation, and calcium transport refers only to the process whereby calcium is transported actively across the vesicle membrane. 3 Dr. Janis was a Fellow of the Canadian Heart Foundation, and his present address is Department of Physiology, Northwestern University Medical School, Chicago, IL 60611 (USA). the plasma membrane of SHR arteries has calcium-binding and -transport properties that are different from those of NWR. However, there is not a complete correlation between the reported effects of the cations on contraction of other arteries in hypertension and on calcium uptake by membranes of SHR and NWR.