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The inspiration for this verse may be drawn from the enumeration pattern at the beginning of the Old Testament book of Ezekiel. Agreeing, the father seeks to tell the "second mother," but she is with the "seventh son," on Highway 61. Verse 4 is about the "fifth daughter" who on the "twelfth night" told the "first father" that her complexion is too pale. "Louie the King" solves the problem with Highway 61. In the third verse, "Mack the Finger" has the problem of getting rid of particular absurd things: "I got forty red white and blue shoe strings / And a thousand telephones that don't ring".
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Georgia Sam may be a reference to Piedmont blues musician Blind Willie McTell, who occasionally went by Georgia Sam when recording.
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Verse 2 describes a poor fellow, Georgia Sam, who is beyond the helping of the welfare department. Abram, the original name of the biblical Abraham, is the name of Dylan's own father. This stanza refers to Genesis 22, in which God commands Abraham to kill one of his two sons, Isaac. God wants the killing done on Highway 61. In Verse 1, God tells Abraham to " kill me a son". In each stanza, someone describes an unusual problem that is ultimately resolved on Highway 61. The junction of highway 61 and highway 49 in Mississippi is said to be the infamous "crossroads" where bluesman Robert Johnson allegedly sold his soul to the devil in exchange for talent and fame. It was a major transit route out of the Deep South particularly for African Americans traveling north to Chicago, St Louis and Memphis, following the Mississippi River valley for most of its 1,400 miles (2,300 km). Highway 61 runs from Duluth, Minnesota, where Bob Dylan grew up in the 1940s and 1950s down to New Orleans, Louisiana.