In this study, the endoplasmic Ca2+ transport ATPase of blood platelets was compared with the Ca2+ ATPase of sarcoplasmic reticulum skeletal muscle. Similar to the muscle enzyme, the Ca2+ ATPase from platelets was found to catalyse an ATP<-->P(i) exchange both in the presence and in the absence of a transmembrane Ca2+ gradient. When platelet vesicles are loaded with Ca2+ and diluted in medium containing ADP, P(i) and EGTA, the ATPase catalyses Ca2+ efflux coupled to synthesis of ATP. The stoichiometry between Ca2+ ion released and ATP synthesized by platelet Ca2+ ATPase is 1, while that of skeletal muscle is 2. Thapsigargin, a specific inhibitor of sarcoplasmic/endoplasmic reticulum Ca2+ ATPases, inhibited both the Ca(2+)-dependent ATPase activity and the reversal of the platelet Ca2+ pump. The possibility is discussed that the differences observed between the two transport systems is related to the distinct amino acid sequences of the enzymes.