The apostle Paul applies the principle from Galatians 4:29 to the situation in the church of God. The epistle to the Galatians focuses on the bitter struggle between the young church of God and the old and venerable religion of the Jews, who had been persecuting Christian converts to some extent for nearly twenty years. Paul writes to a congregation on the verge of being pulled into Judaism into justification by works rather than by grace. He feared that the persuasions of the Jews, which included threats of or real persecution, would sway some or even many of them into recanting their conversion. For this reason he mentions that Ishmael persecuted Isaac. Just as the child of the flesh persecuted the child of promise, the spiritual children of God can expect persecution from those living according to the flesh, especially those whom God has rejected in favor of His elect. Their human nature compels them to strike out at their supplanters in a futile effort to maintain their supposed divine favor.

Persecution from the Jews was a regular part of the apostles' labor in spreading the gospel. Paul received forty stripes minus one from the Jews five times, and he faced perils from his own countrymen as well as from Gentiles and false brethren. Luke, as Paul's nearly constant companion and physician, was an eyewitness to persecution by Gentiles and Jews alike who sought to distort or destroy the truth of Jesus Christ and to continue in the traditions of men. He very possibly shared some of the same trials and at the least tended Paul's wounds and needs. At Thessalonica, Paul reasoned from the Scriptures for three Sabbaths, and the Jews who were not persuaded became envious. They gathered evil men from the marketplace, formed a mob, set the city in an uproar, and attacked the house of Jason. They dragged Jason and some brethren before the rulers, falsely charging that these men who had turned the world upside down acted contrary to Caesar's decrees by saying there was another king, Jesus. Hospitality like Jason's is costly, and so are all the gifts God gives, because the work of God's people turning the world upside down brings trouble and trials now. Yet God's plan is on course, His gifts are irrevocable, and God notices the humble who tremble at His Word. Nothing, including tribulation, persecution, or peril, can separate God's people from the love of Christ.

Jesus experienced hatred to the point of death in His homeland, Judea, and that hatred continued in the persecution of His disciples after His crucifixion. A leader among those persecutors was Saul, later the apostle Paul, whom Jesus converted on the road to Damascus as he traveled to persecute more Christians. The Gentile world proved just as anti-God as the Jewish world had been toward Jesus and the early evangelists, since Gentiles also possessed carnal natures. Trouble also arose inside the church when some Jewish converts could not accept Jesus as High Priest under the New Covenant. They reasoned that angels, as mighty, seemingly eternal spirit beings who move between heaven and earth, outmatched a mortal man they had seen walking about Judea. Above all, He had died on a Roman stake, accursed according to Deuteronomy 21:22-23 and Galatians 3:13-14. Their reasoning seemed logical to human minds but was tragically flawed, because they wholly underestimated Him. Jesus was both divine and human, born of a woman but Son of the eternal God, and as Creator He made the angels. Acts 15 suggests that many of these objectors repented once the details of His origin were presented and decided in council. Only a relatively small number of Jews in the early church held this objection.