Two patients with chronic granulomatous disease had obstructive lesions of the gastrointestinal tract, esophagus, and genitourinary tract, which were successfully treated with corticosteroids. These obstructive lesions, caused by local granuloma formation, have been reported in 18 other patients with chronic granulomatous disease, none of whom received steroids. Our first patient, a 3-year-old boy, had emesis and weight loss associated with antral narrowing and delayed gastric emptying at age 2 years. Antibiotic therapy was ineffective, but intravenous and oral corticosteroid therapy for 10 weeks resulted in clinical cure. One year later, dysuria associated with bladder neck obstruction was also treated successfully with corticosteroids. The second child, a 10-year-old boy, had dysphagia caused by distal esophageal stenosis. Corticosteroid therapy (with concomitant antibiotics) on two occasions reversed this obstruction. Granulomatous cystitis with ureteropelvic obstruction then developed, which also responded to treatment with corticosteroids and antibiotics. Despite the risk of increased susceptibility to infection, corticosteroid therapy is justified in preventing life-threatening obstruction of vital organs.