The Ca ++ transport mechanism in the red cell membrane was studied in resealed ghost cells. It was found that the red cell membrane can transport Ca ++ from inside the cell into the medium against great concentration gradient ratios. Tracing the movement of 45Ca infused inside red cells indicated that over 95 % of all Ca ++ in the cells was transported into media in 20 min incubation under the opdmum experimental conditions. The influence of temperature on the rate constant of transport indicated an activation energy of 13,500 cal per mole. The optimum pH range of media for the transport was between 7.5 and 8.5. As energy sources, ATP, 1 CTP, and U T P were about equally effective, G T P somewhat less effective, and ITP least effective among the nucleotides tested. The Ca ++ transport does not appear to involve exchange of Ca ++ with any monovalent or divalent cations. Also, it is not influenced by oligomycin, sodium azide, or ouabain in high concentrations, which inhibit the Ca ++ transport in mitochondria or in sarcoplasmic reticulum. In these respects, the Ca ++ transport mechanism in the red cell membrane is different from those of mitochondria and the sarcoplasmic reticulum.T h e energy-linked transport of Ca ++ in phosphorylating m i t o c h o n d r i a and in the sarcoplasmic r e t i c u l u m has been well-established d u r i n g the past d e c a d e (Brierley, 1963;Brierley et al., 1964; E n g s t r o m and D e Luca, 1964; D e L u c a and Engstrom, 1961;Chance, 1965;Hasselbach, 1964; Hasselbach a n d Makinose, 1961; Ebashi and L i p m a n n , 1962; Lee, 1965; Lee et al., 1966). Since the free Ca ++ concentration gradient between extra-and intracellular fluid is e x t r e m e l y large in tissues such as muscle and nerve, the existence of a similar Ca ++ p u m p m e c h a n i s m in the cell m e m b r a n e which is responsible for Ca ++ extrusion f r o m these cells against an electrochemical gradient has been suggested ( R e u t e r and Seitz, 1968;Baker et al., 1969). H o w e v e r , no direct evidence was available for an active, o u t w a r d Ca ++ transx ATP, adenosinetriphosphate; CTP, cytidine triphosphate; ITP, inosine triphosphate; GTP, guanosine triphosphate; UTP, uridine triphosphatc.