Returned from combat, Tayo, a mixed-blood Laguna, struggles to regain his health and mental equilibrium. Suffering from what his physicians term "battle fatigue" and the lingering effects of malaria, Tayo had become dysfunctional when he was ordered to shoot several of the enemy and sees in them the faces of his own ancestors.

Later, at the VA hospital, Tayo is told by white doctors to avoid "Indian medicine" and to remove himself as far as possible from his community and heritage. He is heavily sedated and experiences himself as "white smoke."

After he leaves the hospital and returns to his aunt and her family, Tayo's illness worsens (including chronic nausea and vomiting, hallucinations, and weeping). Finally his grandmother calls in a traditional healer who starts Tayo on an intense journey of inner healing (and encounters with other Native American healers) and reconnection with his painful but rich past.