Written by Brian K. Vaughan (Lost, EX MACHINA), this is the saga of Yorick Brown - the only human survivor of a planet-wide plague that instantly kills every mammal with a Y chromosome. Accompanied by his pet monkey, Yorick searches for his lost love...and the answer to why he's the last man on earth.
A crazed woman tries to get a female police officer to help two dying boys. The officer refuses and puts a gun to her head. She explains that all the men are dead.
29 Minutes Earlier: Yorick Brown hangs upside down in a straight jacket in his New York apartment while talking to his girlfriend Beth. The two are separated while she enjoys time in Australia. He rambles about Elvis until Beth finally gets him to quit stalling and admit that he didn't get his latest applied-for job. He asks Beth to hold as he clicks over to pick up another call from his mother.
Yorick's mother, Representative Jennifer Brown, is blown off by her son when she asks about his last interview. She hangs up the phone and gets approached by Senator looking for her vote on an abortion amendment. She refuses and things get a little testy. He is called away to meet with the president about "355."
Yorick is back on the phone with Beth and she senses that he is nervous about something. He nearly tells her but gets interrupted by his pet monkey, Ampersand. He explains to her that the monkey came from a Boston organization and was supposed to help him with chores. Yorick tries to talk to Beth again but Ampersand turns on the television to a report by Christopher Emanuel from Israel.
In Israel, the reporter wraps up and watch as a female Israeli soldier fires rubber bullets at Palestinians. She orders them away but Christopher, seeing an angle for a story he needs, asks her to escort the news team in exchange for an interview. She reluctantly obliges and gives her name as Tse'Elon.
The conversation between Yorick and Beth continues: He admits that he is having a hard time getting out some days. She mocks his fear of the outside world.
Outside in the world, a secret agent drops in on Dr. Frozan Hamad in Jordan. Agent 355 wants to help the refugee doctor escape but is rebuffed. Dr. Hamad isn't afraid of sticking up for her ideals but Agent 355 explains that an amulet is what enemies are after. The doctor explains that the amulet around her neck is a worthless story, one that claims that if the amulet were to leave the country then bad things would happen. She is soon shot down and Agent 355 kills the attackers. She takes the amulet and flees.
Yorick begins rambling about how much he misses Beth. She stops him to tell him something.
In a Boston hospital, genetics scientist Dr. Mann asks for help in having a baby delivered. The doctor she sees first is a student from a class she had taught. He is shocked to learn that the baby is a clone. He is ethically opposed to helping deliver a clone but morally opposed to letting a baby die.
Elsewhere in Boston, Hero Brown, Yorick's sister, tries to get it on in an ambulance with her new firefighter boyfriend. He gets called out, however, and they promise to get together later.
Back on the phone, Yorick stops Beth from telling him whatever it was going to be and admits that he may have bought a little something for her. He bought a magic ring and proposes to her over the phone.
At that moment, his mother's assistant Darin dies, as does Christopher Emanuel and his news crew in Israel, Agent 355's male pilot in Jordan, Hero's boyfriend, and every male mammal on the Earth. Except Yorick - who awaits Beth's answer - and Ampersand.