Prolonged recordings of esophageal motility have shown that dynamic changes of lower esophageal sphincter (LES) pressure such as transient LES relaxation and LES pressure drifts are the most common mechanisms underlying gastroesophageal reflux (GER). The coexistence of a delayed gastric emptying has also been reported in a high proportion of patients with reflux disease. However, not much information is available on the effects of antireflux therapy on the pathogenetic mechanisms of GER. The purpose of this study was to determine in a group of children with severe reflux disease the effect of omeprazole therapy on motor changes of LES underlying GER as well as on gastric emptying time. Twenty-two children (median age: 6.6 years) with GER disease, refractory to combined ranitidine and cisapride administration, entered into an eight-week omeprazole course. Ten subjects with moderate GER disease served as controls (median age: 6.0 years). Before and after omeprazole administration, the following variables were assessed: esophagitis grading, fasting and fed simultaneous prolonged recording of distal esophageal sphincter pressure (with a sleeve catheter) and intraesophageal pH, LES and esophageal peristalsis amplitude, and gastric emptying time of a mixed solid-liquid meal (measured with gastric ultrasound). As compared to controls, patients showed a higher rate of transient LES relaxation and LES pressure drift (P < 0.01), a reduced amplitude of basal sphincter pressure (P < 0.01) and peristalsis (P < 0.05), and a more prolonged gastric emptying time (P < 0.05). After ending omeprazole, there was no significant change in any of the motor abnormalities of the esophagus and in gastric emptying time despite a marked improvement of symptoms and esophagitis in all patients. Sixteen patients were symptomatic when reevaluated on a clinical basis two months after ending therapy. We conclude that in children with severe GER disease, an abnormally high rate of both transient LES relaxation and LES pressure drift and slow gastric emptying are not affected by omperazole treatment, even though esophageal mucosal damage is markedly improved or cured. These abnormalities represent a primary motor disorder and can be implicated in the refractoriness of reflux disease.