The effect of resection of 75% (length measurement) of the large colon in ponies was studied. Ten ponies in good physical condition were divided into two groups: group I consisted of the six experimental ponies and group II of four control ponies. Preoperatively and postoperatively for five months, ten clinicopathological parameters were determined: body weight, venous blood pH, plasma bicarbonate, total plasma protein concentration, serum electrolyte values (sodium, potassium, chloride), and fecal osmolarity. Subjective assessment of attitude and appetite revealed no difference between the groups or within groups at any time. Resection of a major portion of the large colon did not significantly influence the clinicopathological parameters evaluated. The hematocrit of the ponies in group I did decrease during the first postoperative month and this was attributed to whole blood loss associated with the resection procedures. The results of this investigation indicated that resection of 75% of the large colon in ponies is compatible with life.