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The split between the Northern and Southern Baptist organizations was over slavery and education of slaves, and by the 18th century, about 40 percent of Southern Baptist preachers in South Carolina owned slaves. At the time of the split, the Southern Baptist group used the curse of Cain as justification of the practice. In fact, most 19th and early 20th century Southern Baptist congregations in the southern United States taught that there were two separate heavens; one for blacks, and one for whites.

The doctrine was used to support a ban on ordaining blacks to most Protestant clergies until the 1960s in the U.S. and Europe. The Coptic, Ethiopian, Orthodox, Thomasite and the Catholic church did not recognize these interpretations and did not participate in the religious movement to support them. Certain Catholic Diocese in the Southern United States did adopt a policy of not ordaining blacks to oversee, administer sacraments to, or accept confessions from white parishioners. This policy was not based on a Curse of Cain teaching, but was justified by any possible perceptions of having slaves rule over their masters. (Dictionary of African-American Slavery)

Baptists and other denominations including Pentecostals officially taught or practiced various forms of racial segregation well into the mid-to-late-20th century, though all races were accepted to worship services after the 1970s and 1980s when many official policies were changed. In fact, it wasn't until 1995, that the Southern Baptist Convention officially renounced its "racist roots." Nearly all Protestant groups in America had supported the notion that black slavery, oppression, and African colonization was the result of God's curse on people with black skin or of African descent through Cain or through the curse of Ham, and some churches practiced racial segregation as late as the 1990s, including Pentecostalism. Today, however, official acceptance and practice of the doctrine among Protestant ogranizations is limited almost exclusively to churches connected to white supremacy, such as the Aryan World Church and the New Christian Crusade Church.