It is uncertain to what degree sensation and pain relating to the gut are influenced by sex. The aim of the study was to explore sex differences to experimental multimodal stimulation of the esophagus in 22 age-matched males and females. A probe was positioned in the lower part of the esophagus. Mechanical stimuli were applied as distensions with a bag using an impedance planimetric method. The distensions were done before and after relaxation of the smooth muscle. Thermal stimulation was done with recirculating water at 1 and 60 degrees C in the bag. The sensory intensities were assessed during the stimulations, and the referred pain area was drawn at maximum pain intensities. An increased sensation to mechanical stimuli was found in the males for volume, pressure, and tension (P = 0.003, P = 0.02, P = 0.005), whereas cross-sectional area and strain showed no sex difference (P = 0.06, P = 0.9). Sex differences were not found for the cold and warmth stimulations (P = 0.6, P = 0.1). The mean size of the referred pain areas to the different stimuli was 23.6 cm2 in males and 48.7 cm2 in females (P = 0.002). As strain is believed to be the major determinant for the sensory response to mechanical stimulation of the gut, we conclude that no robust sex differences were observed in the assessments of the multimodal stimulations. However, the larger referred pain area in females reflects sex differences in central pain processing, which may explain the female preponderance in functional disorders relating to the gut.