The basis of any dosage adjustment is a suffciently close correlation between dose and response of the drug. Measurement of pharmacodynamic effects in clinical pharmacology make a first judgement on different therapeutic doses possible and, under safety aspects, on different side effects of a drug. It is generally accepted that these investigations involving healthy volunteers have to be restricted to noninvasive methods. Therefore, a number of noninvasive methods has been established during the last years. Compared to the direct measurements routinely used in clinical practice, the noninvasive methods are often thought to be less sensitive and subject to major variation. Noninvasive methods in clinical pharmacology must be easy to perform, safe, and tolerable to the volunteers for repeated measurements. The data obtained have to be reliable and highly reproducible. Furthermore, it is necessary to know that the effects measured in healthy volunteers by these methods are transferable to patients. Last, but not least, the method must be accepted by international experts and should not be too expensive. Due to the direct accessibility of the esophagus, esophageal manometry is technically easy to perform and is well-tolerated by the subject. Several methodological and physiological factors such as sensor and body position, age, and the mode of eliciting peristaltic pressure waves may influence esophageal pressure recording and must be considered in order to obtain reproducible and comparable results. Furthermore, it has been shown that all drugs used therapeutically in esophageal motility disorders also show an effect in healthy volunteers measurable by esophageal pharmacomanometry. Therefore, this method is useful in clinical pharmacology for dose-response studies of drugs influencing the lower esophageal sphincter pressure (LESP) and the motility in the gastrointestinal tract. It could be shown in healthy volunteers and in patients with gastroensophageal reflux that the LESP is increased dose dependently by rising doses of metoclopramide, bromopride, domperidone, and cisapride. The therapeutic usefulness and effectiveness of these drugs has been shown in adequate and well-controlled clinical studies. On the other hand, it could be demonstrated that anticholinergic agents, adrenoreceptor agonists, nitrates, and calcium antagonists decrease the LESP and the motility in the gastrointestinal tract. Currently, perhaps the most interesting pharmacological therapy of the classic esophageal motility disorders is the use of calcium antagonists. Nifedipine, for example, decreased the LESP as well as the amplitude and duration of contractions in the esophageal body in a dose-dependent manner after a single oral administration of 10–40 mg. The influence of nifedipine on esophageal motility parameters also was marked after repeated administration. Furthermore, this method has shown usefulness for assessment of safety or new indications of drugs used for other diseases like anesthetics, β-agonists, anticholinergics, calcium antagonists, or prostaglandins.