Our goal was to investigate associations between the status of interstitial cells of Cajal (ICC) and electrogastrogram (EGG) parameters, gastric emptying and symptoms in a large cohort of patients with gastroparesis. Forty-one patients with refractory gastroparesis who were referred for gastric electrical stimulation (GES) underwent full thickness gastric (antrum) biopsy during the surgery to place the GES device. The biopsy samples were stained with c-kit and scored for the presence of ICC based on criteria obtained from 10 controls. All patients underwent EGG recordings, a 4-h standardized scintigraphic gastric emptying study and symptom assessment prior to the surgery. Based on antral biopsy, 15 patients (36%) had almost no ICC (ICC- group) and 26 patients had adequate cell numbers (ICC+ group). EGG recordings in the ICC- group displayed significantly less normal slow waves than in the ICC+ group both in the fasting and fed states. Tachygastria in the ICC- group was significantly more than in the ICC+ group both in the fasting (32 +/- 8%vs 11 +/- 2%) and fed states (27 +/- 9%vs 12 +/- 2%). There was no statistical difference in gastric emptying, symptom severity of gastroparesis, aetiology, age and gender between the two groups. Severely depleted ICC occurs in up to 36% of gastroparetic patients and significantly correlates with an abnormal EGG. Severely depleted ICC does not correlate with the severity of gastroparesis as assessed by gastric emptying or symptom status but did result in a poorer symptomatic response to GES. These data suggest that the EGG may have a role for predicting ICC status during clinical evaluation of gastroparetic patients.