To evaluate the frequency, etiology, and outcome of diffuse interstitial pneumonitis after treatment of children with Stage IV (favorable histologic type) Wilms' tumor using whole-lung and abdominal radiation therapy, and combination chemotherapy, all cases reported in such patients entered on National Wilms' Tumor Study 3 were reviewed. Diffuse interstitial pneumonitis was reported in 13.0% of patients. The etiology was varicella, one patient; Pneumocystis carinii, three patients; and unknown, 15 patients. The time elapsed after the completion of whole-lung irradiation did not distinguish those patients with pneumonitis due to P. carinii from those with pneumonitis of unknown etiology. All three children with pneumonitis due to P. carinii survived the episode, whereas only four of 15 (27%) patients with pneumonitis of unknown etiology survived the episode. Management of Wilms' tumor patients who develop diffuse interstitial pneumonitis after whole-lung irradiation should include a diagnostic procedure known to be sensitive for the diagnosis of P. carinii infection.