Set in Baltimore, Maryland, the plot revolves around Macon Leary, a writer of travel guides whose son has been killed in a shooting at a fast-food restaurant. He and his wife Sarah, separately lost in grief, find their marriage disintegrating until she eventually moves out. When he becomes incapacitated due to a fall, he returns to the family home to stay with his eccentric siblings - sister Rose and brothers Porter and Charles - whose odd habits include alphabetizing the groceries in the kitchen cabinets and ignoring the ringing telephone. When his publisher, Julian, comes to visit, Julian finds himself attracted to Rose. They eventually marry.
Macon hires Muriel Pritchett, a quirky young woman with a sickly son, to train his unruly dog, and soon finds himself drifting into a relationship with the two of them. When his wife Sarah becomes aware of the situation, she decides they should reconcile, forcing him to make a difficult decision about his future.
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