Brilliant brothers Langley and Homer Collyer are born into bourgeois New York comfort in settled times, their home a fin-de-siècle mansion on upper Fifth Avenue, their future rosy. But before he is out of his teens Homer begins to lose his sight, Langley returns from the War in Europe with his lungs seared by gas, and when the death of their parents in the influenza epidemic of 1918 leaves the brothers orphaned, they seem perilously ill-equipped to deal with the new era.
Around Central Park carriages give way to motor cars, Prohibition to free love, but Homer and Langley adapt: their townhouse fills and empties and fills again, with servants, lodgers, tea-dancers and gangsters. They are mocked and spied on, embraced by hippies and besieged by bailiffs, but as the world turns ever more incomprehensible Homer and Langley hold fast to their principles of self-reliance, courage, kindness and love, and they endure.