Microsomal fractions were isolated from gastric antrum and fundus smooth muscle of guinea pigs. Ca2+ uptake into and Ca2+ release from the membrane vesicles were studied by a rapid filtration method, and Ca2+ transport properties of the different regions of the stomach were compared. ATP-dependent Ca2+ uptake was similar in microsomes isolated from both regions. This uptake was increased by oxalate and was not affected by NaN3. Oxalate affected Ca2+ permeability of both antrum and fundus microsome vesicles similarly. Fundus microsome vesicles preincubated in 100 mM NaCl and then diluted to 1/20 concentration with Na+-free medium had significantly higher ATP-independent Ca2+ uptake than vesicles preincubated in 100 mM KCl and treated the same way. This was not true for antrum vesicles. Monensin abolished Na+-dependent Ca2+ uptake, and NaCl enhanced Ca2+ efflux from fundus microsome vesicles. The halflife values of Ca2+ loss from fundus vesicles in the presence of NaCl were significantly smaller than those in the presence of KCl. The release of Ca2+ from the vesicles within the first 3 min was accelerated by NaCl to three times that by KCl. However, NaCl had no effect on Ca2+ release from antrum microsome vesicles. Results suggest two distinct mechanisms of stomach membrane Ca2+ transport: (1) ATP-dependent Ca2+ uptake and (2) Na+-Ca2+ exchange; the latter in the fundus only.