Summary The Megacolon‐Syndrome is a hereditary disease of homozygous spotted rabbits (En En). Investigations have been performed on some special traits related to functional aspects of the gut in comparison to vital heterozygous spotted rabbits (En en). It was found that En En rabbits showed significantly reduced sodium absorption rates across the wall of the cecum. Consequently, the dry matter content of the ingesta was reduced at this location, whereas the content of the ashes was increased. These results indicate that a further important pathogenetic aspect of this hereditary disease is an undue liquification of ingesta in proximal parts of the large intestine. Severe clinical problems, however, resulted from obstipation. This is concluded to be a late complication due to and modified by different stressors of endogenic and exogenic origin. Thus there are some indications that an early site of spot‐gene related effects might be the small intestine. This segment of the bowel was shorter and had an increased dry matter proportion of its wall when compared with heterozygous spotted rabbits. But a decreased proportion of dry matter within the wall of the large intestine was found. The latter could be an effect of the hypothyreotic state of metabolism in En En rabbits.