The “40-Year-Old Virgin” guys have swapped Anne Hathaway for “Grey’s Anatomy” star Katherine Heigl.

The actress has signed up for writer/director Judd Apatow’s “Knocked Up,” according to The Hollywood Reporter.

The project stars “Virgin” actor Seth Rogan as a man who has a one-night stand with a woman (Heigl) and gets her pregnant. Other “Virgin” actors reuniting with their fearless leader are Paul Rudd and Leslie Mann, who’s married to Apatow.

Hathaway, known for “The Princess Diaries” and “Brokeback Mountain,” reportedly left because of creative reasons. She next stars opposite Meryl Streep in the big-screen adapation of “The Devil Wears Prada,” hitting theaters in June.

Heigl, 27, is best known for playing hot surgical intern Isobel in ABC’s chick medical drama “Grey’s Anatomy.” Before that, she played another Isabel, a teenage alien this time, in the WB’s “Roswell.”

Her big screen credits include “Bride of Chucky,” “100 Girls,” “Valentine” and “The Ringer” with Johnny Knoxville.