Jackhammer esophagus (JE) is a hypercontractile disorder, the pathogenesis of which is incompletely understood. Multiple rapid swallows (MRS) and rapid drink challenge (RDC) are complementary tests used during high-resolution manometry (HRM) that evaluate inhibitory and excitatory neuromuscular function and latent obstruction, respectively. Our aim was to evaluate esophageal pathophysiology using MRS and RDC in 83 JE patients (28 men; median age: 63 yr; IQR: 54-70 yr). Twenty-one healthy subjects (11 men; median age: 28 yr; range: 26-30 yr) were used as a control group. All patients underwent solid-state HRM with ten 5-ml single swallows (SS) and one to three 10-ml MRS; 34 patients also underwent RDC. Data are shown as median (interquartile range). Abnormal motor inhibition was noted during at least one MRS test in 48% of JE patients compared with 29% of controls ( P = 0.29). Mean distal contractile integral (DCI) after MRS was significantly lower than after SS [6,028 (3,678-9,267) mmHg·cm·s vs. 7,514 (6,238-9,197) mmHg·cm·s, P = 0.02], as was highest DCI ( P < 0.0001). Consequently, 66% of JE patients had no contraction reserve. At least one variable of obstruction during RDC (performed in 34 patients) was outside the normal range in 25 (74%) of JE patients. Both highest DCI after SS and pressure gradient across the esophagogastric junction (EGJ) during RDC were higher in patients with dysphagia versus those without ( P = 0.04 and 0.01, respectively). Our data suggest altered neural control in JE patients with heterogeneity in inhibitory function. Furthermore, some patients had latent EGJ obstruction during RDC, which correlated with the presence of dysphagia. NEW & NOTEWORTHY Presence of abnormal inhibition was observed during multiple rapid swallows (MRS) in some but not all patients with jackhammer esophagus (JE). Unlike healthy subjects, JE patients were more strongly stimulated after single swallows than after MRS. An obstructive pattern was frequently observed during rapid drink challenge (RDC) and was related to presence of dysphagia. MRS and RDC during high-resolution manometry are useful to show individual pathophysiological patterns in JE and may guide optimal therapeutic strategies.