[Griff]

According to wiki:

The song has five stanzas. In each stanza, someone describes an unusual problem that is ultimately resolved on Highway 61. In Verse 1, God tells Abraham to "kill me a son". God wants the killing done on Highway 61. This stanza references Genesis 22, in which God commands Abraham to kill one of his two sons, Isaac. Abram, the original name of the biblical Abraham, is the name of Dylan's own father. Verse 2 describes a poor fellow, Georgia Sam, who is beyond the helping of the welfare department. He is told to go down Highway 61. Georgia Sam may be a reference to Piedmont blues musician Blind Willie McTell, who occasionally went by Georgia Sam when recording.

In the third verse, a "Mack the Finger" has this 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". "Louie the King" solves the problem with Highway 61. Verse 4 is about the "fifth daughter" who on the "twelfth night" told the "first father" that her complexion is too pale. Agreeing, the father seeks to tell the "second mother", but she is with the "seventh son", on Highway 61.

The fifth and last verse is the story of a bored gambler, trying "to create the next world war". His promoter tells him to "put some bleachers out in the sun / And have it on Highway 61". There is an evident political undertone in this absurd tale.

There is a pause in each verse while Dylan waits for some event in the story to finish; in the third verse, for example, the pause occurs while Louie the King attempts to resolve the shoestring-and-telephones problem. Between each verse Dylan is heard blowing an imitation police whistle, known as a "Siren Whistle" [1], brought in by Sam Lay who was drummer on the Highway 61 sessions as noted by Tony Glover in the liner notes to Live 1966. Other accounts say that the whistle was brought in by Al Kooper. It is said that he had originally brought in the "siren whistle" to police the sessions. Supposedly, if someone were to begin doing drugs he would go into a corner and blow on the whistle. He later suggested to Dylan that he use the whistle in this song instead of his harmonica.