After birth, the normoxic muscle media of the ductus arteriosus (DA) becomes profoundly hypoxic as it constricts and undergoes anatomic remodeling. We used isolated fetal lamb DA (pretreated with inhibitors of prostaglandin and NO production) to determine why the immature DA fails to remain tightly constricted during the hypoxic phase of remodeling. Under normoxic conditions, the mature DA constricts to 70% of its Maximal Active Tension (MAT)). Half of its normoxic tension is due to Ca⁺⁺ entry through Ca_L-channels and SOC-channels. The other half is independent of extracellular Ca⁺⁺ and is unaffected by inhibitors of SR Ca⁺⁺ release (ryanodine) or reuptake (cyclopiazonic acid (CPA)). The mature DA relaxes slightly during hypoxia (to 60% MAT) due to decreases in Ca_L-channel-mediated Ca⁺⁺ entry. Inhibitors of Rho-kinase and tyrosine-kinase inhibit both Ca⁺⁺-dependent and Ca⁺⁺-independent DA tension. Although Rho-kinase activity may increase during gestation, the immature DA develops lower tensions than the mature DA primarily because of differences in the way it processes extracellualar Ca⁺⁺. CaL channel expression increases with advancing gestation. Under normoxic conditions, differences in Ca_L-channel-mediated Ca⁺⁺ entry account for the differences in tension between immature (60% MAT) and mature (70% MAT) DA. Under hypoxic conditions, differences in both CaL-channel-dependent and Ca_L-channel-independent extracellular Ca⁺⁺ entry, account for the differences in tension between immature (33% MAT) and mature (60% MAT) DA. Stimulation of extracellular Ca++ entry through reverse mode Na⁺/Ca⁺⁺ exchange or CPA-induced SOC channel activity constrict the DA and eliminate the differences between immature and mature DA during both hypoxia and normoxia.