Meconium ileus was noted as an early manifestation of cystic fibrosis in 60 neonates between 1972 and 1991. There were 20 girls and 40 boys. A family history of cystic fibrosis was present in six children. Twenty-five neonates had uncomplicated meconium ileus due to inspissated meconium within the terminal ileum. Thirty-five neonates presented with 56 complications of meconium ileus, including volvulus (n = 22), atresia (n = 20), perforation (n = 6), and giant cystic meconium peritonitis (n = 8). Clinical presentation included abdominal distension, bilious vomiting, and failure to pass meconium. In two recent cases, prenatal ultrasonography detected a mass with proximal bowel distension indicative of cystic meconium peritonitis. Mechanical bowel obstruction in the other neonates was diagnosed from plain abdominal radiographs and barium enema. Ten patients with uncomplicated meconium ileus were successfully treated with a diatrizoate meglumine (Gastrografin) enema. The remaining 15 patients required a laparotomy, with 9 treated by bowel resection and enterostomy and 6 recent cases managed with enterotomy and irrigation. Complicated cases were managed by bowel resection and anastomosis (n = 15) or enterostomy (n = 20). Survival at 1 year was 92% in patients with uncomplicated meconium ileus and 89% for those with complicated meconium ileus. The therapy of choice for uncomplicated meconium ileus is nonoperative Gastrografin enema, with enterotomy and irrigation reserved for enema failures. Complicated cases require exploration and, in the absence of giant cystic meconium peritonitis, are usually amenable to bowel resection and primary anastomosis.