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Homer Wells grows up in an orphanage where he spends his childhood "being of use" as a medical assistant to the director, Dr. Wilbur Larch, whose history is told in flashbacks: After a traumatic misadventure with a prostitute as a young man, Wilbur turns his back on sex and love, choosing instead to help women with unwanted pregnancies give birth and then keeping the babies in an orphanage. He makes a point of maintaining an emotional distance from the orphans, so that they can more easily make the transition into an adoptive family, but when it becomes clear that Homer is going to spend his entire childhood at the orphanage, Wilbur trains the orphan as an obstetrician and then comes to love him.
Wilbur's and Homer's lives are complicated by the fact that the former is also secretly an abortionist. Wilbur comes to this work reluctantly but is driven by seeing the horrors of back-alley operations but Homer, when learning about this secret, considers it morally wrong.
Homer befriends a young couple, Candy Kendall and Wally Worthington, who work in an apple orchard, and leaves the orphanage with them. Wally and Homer become best friends and Homer develops a secret love for Candy. Then Wally goes off to war and his plane is shot down over Burma. He is presumed missing by the military, but Homer and Candy both think that he is dead and move on. They have sexual relations and Candy becomes pregnant. They go back to St. Cloud's Orphanage, where their child is born and named Angel. Candy becomes the first mother to take her own child home with her.
Subsequently, Wally is found in Burma and returns home, paralyzed from the waist down. He is still able to have sexual intercourse but is sterile because of an infection received in Burma. They lie to the family about Angel's parentage, claiming that Homer decided to adopt him. Wally and Candy marry shortly afterward, but Candy and Homer maintain a secret affair that lasts some fifteen years.
Many years later, teenage Angel falls in love with Rose Rose, the daughter of the head migrant worker at the apple orchard, who becomes pregnant with her father's child, and Homer performs an abortion on her. Homer decides to return to the orphanage after the death of Dr. Larch, to work as the new director. He decides that he provides the safest abortion alternative for women and that all of his work will be "the Lord's work".
A subplot of the novel follows the character Melony, who grew up alongside Homer in the orphanage. She was Homer's first girlfriend in a relationship of circumstances. After Homer leaves the orphanage, so does she in an effort to find him. She eventually becomes an electrician and takes a female lover, Lorna. Melony is an extremely stoic woman, who on one occasion refuses to press charges against a man who brutally broke her nose and arm so that she can later retaliate herself. She is also the catalyst of Homer's transformation from his comfortable but not entirely admirable position at the apple orchard to becoming Dr. Larch's replacement at the orphanage.
