The Blood of A Most Holy Man is the blood of a man who is especially holy such as a saint or other highly religious and good person.
Searching for the ingredients for the spell, Sam comes to the conclusion that the most likely source of such blood is a saint. On the Internet, Sam locates Margaret Astor, a black market dealer who might possess saint blood. Margaret directs the Winchesters to Richard Greenstreet who claims to have the blood of Saint Ignatius. In exchange for the Winchesters getting him the skull of Saint Peter, Greenstreet promises to provide the Winchesters with the blood.
Following a massive gunfight, the Winchesters and Father Luca Camilleri confront Greenstreet who admits to lying to get them to steal the skull for him. The next morning, as the Winchesters see Luca off, they learn that due to his immense charitable work, the Pope declared that Luca was "a most holy man." Realizing that Luca fit the criteria, the Winchesters requested his blood which Luca provided them with. Afterwards, Dean expressed faith that with the blood, they could succeed in their mission.
In a flashback it was revealed that somehow the Men of Letters came to know of the ritual needed to open a portal to another world. In 1925, after having somehow gathered all of the ingredients one of which was the Blood of A Most Holy Man, rogue Men of Letters member Diego Avila performed the ritual in the Portsmouth, Rhode Island chapter house to bring the gods Yokoth and Glythur from their world to Earth in order to cleanse it and start over. Diego and his followers succeeded in opening the rift and summoning Yokoth who possessed Sandy Porter. Yokoth ate most of the Men of Letters involved, but the survivors managed to close the rift and bound Yokoth who could not be killed.
In 2018, after tracking the Seal of Solomon to the Portsmouth chapter house, the Winchesters inadvertently freed Yokoth. Yokoth later used ingredients stored in a hidden compartment to replicate the ritual to open a rift into her own world and bring Glythur into the Main Universe in the body of Dean Winchester. Sam arrived with Marco and Ophelia Avila before she could succeed. Dean managed to free himself and steal the Seal of Solomon which Ophelia used to close the rift. Before the rift closed, Yokoth was pulled back through by Glythur.
After getting all of the needed ingredients, Sam used the blood along with the fruit, Seal and Gabriel's grace to open a rift to Apocalypse World that Dean traveled through with Arthur Ketch. Once Dean returned, the Winchesters could not repeat the ritual as Gabriel had departed and they had no more of his grace despite having everything they needed.
Awhile later, witch Rowena MacLeod repeated the ritual with Gabriel's grace, but he didn't have enough and the rift fizzled out. After capturing Lucifer, his grace was used to open the rift and keep it open continuously.
- Season 13
- The amount of blood needed for the Demon Tablet Alternate Reality Rift Opening Ritual appears to be small as the Winchesters only got a small bottle of the blood and yet had enough to perform the ritual three different times. In The Thing, Yokoth is only shown to use a small amount of blood as well.
- It is unknown where Michael and Lucifer found the needed blood in Apocalypse World between Exodus and Let the Good Times Roll in order to perform the ritual themselves.