“Enough Said” offers enough bittersweet laughs and rueful wisdom to carry a half-dozen movies. Under the sure guidance of writer/director Nicole Holofcener, Julia Louis-Dreyfus and James Gandolfini play divorced Los Angelinos who strike up a tentative relationship after meeting at a sprawling garden party. At the same event, she meets Catherine Keener, playing one of her trademark bright, difficult women. The two bond quickly, and soon Keener is unloading at length about her insufferable clown of an ex-husband. Then Louis-Dreyfus realizes that her sweet, lovable beau and Keener’s lummox are one and the same.

Keener, a needy, pretentious poet with plenty of admirers but few friends, uses Louis-Dreyfus as an audience for her spiteful reminiscences. The high-strung Louis-Dreyfus, facing an empty nest as her daughter prepares to leave for college, seizes on the new friendship over-eagerly, grateful to feel needed. But Keener’s complaints about Gandolfini’s weight, housekeeping habits and bedroom shortcomings begin to poison Louis-Dreyfus’ perception of the warm and tender man.

Holofcener (“Friends With Money”) wisely chooses not to burden the easygoing film with too much story. “Enough Said” allows us time to develop a relationship with the two actors while they build a connection with each other. The scene where they lie in bed and tenderly catalog each other’s imperfections is the most touching moment of film romance I’ve seen in ages.

Once the characters and (mildly contrived) premise are in place, Holofcener watches the relationships develop. She demonstrates how guilt, habit and inertia can keep us in bad matches, and self-protective fear can keep us out of promising ones. As always, her Los Angeles locations are wonderfully observed, with housing details making quiet points about characters’ status and personality, and the limpid sunlight providing an ironic background for overcast, burdened hearts.

The cast is terrific. Toni Collette plays our heroine’s old friend, a psychotherapist whose flawed marriage (to Ben Falcone, “Bridesmaids’ ” undercover air marshal) proves that even professionals can louse up. Louis-Dreyfus and Gandolfini have made only a handful of films in recent years, and they’re delightful together. They contribute lived-in, vanity-free portraits of fully realized individuals hoping against hope for a new chance at lifelong love. A dedication to the late actor plays over the closing credits, saluting a lost talent whose range we were only beginning to appreciate.