Possible humoral involvement in the control of postresectional intestinal adaptation was tested in individual rats and in pairs of rats connected in vascular parabiosis for 48 hr. In individual rats, transection of the jejunum produced transient mucosal hyperplasia in the mid and distal small intestine, independent of the effect of laparotomy and of handling the bowel. Jejunal resection caused more intense and sustained distal hyperplasia, with increases in midbowel RNA content (38%), DNA content (16%), and DNA specific activity (68%) over values 48 hr after transection. In parabiotic rats, both transection and resection of the jejunum in one partner stimulated mucosal uptake of [H]TdR in the intact parabiont; increments of 59 to 128% in total radioactivity and in specific activity of DNA were found in the mid and distal small intestine of the intact parabiont. Because only rats actually undergoing abdominal operations had higher mucosal nucleic acid contents than their parabiotic partners, the transmitted response was weaker than the direct response. Systemic factors as well as local (topical) stimulators appear to be involved in adaptation of the shortened gut.