Seattle is an acquired taste. Most of us have friends who moved here and didn't even make it a year—they just can't let go of the months of clouds, the wishy-washy mincing dance of a flock of Seattleites around an open bus door, the hours of discussions before any action can be taken. The force that moves the plot of Maria Semple's new novel, Where'd You Go, Bernadette (Little, Brown, $25.99), is Bernadette Fox's hatred of Seattle. A MacArthur "Genius"–winning architect from Los Angeles whose best work is years behind her, Fox moved here because her husband, Elgin Branch, is overseeing the kind of tech project at Microsoft that could, iPhone-like, shift the cultural landscape forever.

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And boy does Fox hate it here in the "dreary upper-left corner." She hates that her husband loves it so much, has become a "bike-riding, Subaru-driving, Keen-wearing alter ego" of his old self. She seethes over the five-way intersections and bucolic drivers, and the simple fact that she lives in a state that borders Idaho. She rages against the homeless people with a snotty, entitled air of wealth ("Why does every beggar have a pit bull?"). She detests Microsoft's creepily aimless culture of world domination. It's gotten so bad that she's practically become a shut-in, secretly acquiring a virtual personal assistant named Manjula to perform all her leaving-the-house duties.

In fact, there's only one place Fox hates more than Seattle. As she writes to Manjula, "Of the million reasons I don't want to go to Antarctica, the main one is that it will require me to leave the house." Fox is facing down a trip to Antarctica because she has promised her daughter, Bee, a trip there if she gets perfect grades. (Like most of Semple's characters, Branch and Fox are what Kurt Vonnegut used to refer to as "fabulously well-to-do.") Rather than going through with the trip—and because her husband is growing increasingly suspicious of her sanity—Fox up and disappears.

Those who have met Semple know that when she moved to Seattle from Los Angeles a few years ago, she was none too thrilled with her new home. She wasn't in love with Los Angeles, where she wrote for TV comedies like Arrested Development and Mad About You, but Seattle's lackadaisical pace inspired a few rants that sound not dissimilar from some of Fox's observations. This personal touch helps make Bernadette even funnier than Semple's debut comic novel, This One Is Mine.

Bernadette is more ambitious, too. It's structured as a patchwork epistolary novel, a compilation of e-mails, letters, and documents sent around a small circle of friends, nemeses, and acquaintances of Fox's, including the terribly self-centered clique of mothers at Bee's private school. You quickly realize that Bee is assembling all the information she can find in order to piece together the reasons behind her mother's disappearance. Bee seems like a precocious kid of the sort common to literary fiction, but there are some nice flourishes of realism spread throughout—her annoyance that her mother likes the Beatles as much as she does, for one—to keep her grounded.

The book stumbles a bit in the middle as it transitions from a scathing anti-Seattle manifesto into a family drama with comic undertones. But once the gears have finished their grinding and the shuddering subsides, Semple eases into her strongest work yet, allowing her characters to change in a way that suits the story, and not just shooting for an easy punch line or a sharply worded barb. In the end, with its big heart set on acceptance, Bernadette feels something like coming home. recommended