We investigated weight gain and clinical course of 14 patients with cystic fibrosis (CF), aged 7 to 23 years, who received long-term nocturnal supplemental feedings by means of percutaneous endoscopic gastrostomies (PEGs). The patients (nine female, five male) were moderately malnourished; the weight-for-height value was 77.8% (SD 6.4%) of the predicted value. Lung function tests revealed severe airway obstruction; mean vital capacity was 46.1% (SD 14.4%), and mean forced expiratory volume in 1 second (FEV1) was 30.8% (SD 12.3%) of predicted value. A nonelemental formula providing 35% of total energy from fat was used for nocturnal feedings. The patients received 800 to 1500 kcal per night by slow intragastric infusions. Enteric-coated pancreatic microsphere preparations were taken orally just before bedtime. After 1 year of supplemental feedings, body weight had increased by 6.0 kg (SD 3.6 kg) and weight-for-height value by 9.0% (SD 6.1%) of predicted compared with baseline values. Lung function also improved significantly: vital capacity increased by 8.2% (SD6.3%) and FEV1 by 3.9% (SD 4.2%) of predicted values (p < 0.01). The total duration of nocturnal feedings was 364 months, or 26 months per patient. Nine of the fourteen patients continue to use the PEG, three patients had the PEG tube removed, and two patients have died 21 and 23 months after PEG insertion. We conclude that nocturnal PEG feedings of malnourished patients with CF improve nutritional status and lung function without major side effects.