Background: Gastrointestinal manifestations are frequently encountered in cystic fibrosis patients. Gastroparesis evidenced by a variety of diagnostic methods has been described in patients with cystic fibrosis, predominantly in children and in individuals with advanced lung disease. The presence of gastroparesis in adult patients with different degrees of lung involvement and its response to the acute and chronic administration of macrolides have not been reported. Methods: Using the University of Florida Cystic Fibrosis database we identified symptomatic patients who had gastroparesis confirmed by a prolonged half-time during gastric emptying scintigraphy. Results: Of 86 cystic fibrosis patients, periodically followed in our institution, we found five who had classical symptoms and prolonged gastric emptying half-time. Age 25.2 ± 8 years, 80% females, BMI 22 ± 9 kg/m2, HbA1c 5.8 ± 0.6 g/dl, FEV1 53.2 ± 15% of predicted. Gastric emptying half-time was 191.4 ± 91.4 min (range 100-300 min) and decreased to 12.2 ± 6 min (range 5-20 min) after IV administration of erythromycin (p = 0.043). Patients were followed up for 3 ± 2.1 years. All patients but one, who was taking opiods, had good clinical response to PO macrolides. Conclusions: Gastroparesis occurs in patients with cystic fibrosis, even in patients with relatively preserved lung function and in those without cystic-fibrosis related diabetes. Macrolides may be an effective therapy in cystic fibrosis patients with gastroparesis when administered acutely or chronically. © 2009 Elsevier B.V. All rights reserved.