Our aim was to determine if extrinsic denervation alters the absorptive response of the colon to proabsorptive and prosecretory stimuli. Ten dogs underwent enteric isolation of a 50-cm proximal colonic segment; five were also randomized to undergo extrinsic denervation (DEN). At 2 and 13 wk postoperatively, net absorptive fluxes (mean ± sem) of water and electrolytes were determined during basal conditions and during proabsorptive low-dose (0.3 μg/kg/min) or high-dose (3 μg/kg/min) norepinephrine or prosecretory VIP (500 pg/kg/min). The net absorptive flux of water under basal conditions was decreased in DEN versus neurally intact controls at two weeks (4.0 ± 0.6 vs 6.6 ± 0.7 μl/min/cm, P = 0.03) but did not differ at 13 weeks (5.0 ± 1.0 vs 5.7 ± 0.9, P > 0.05). Low- and high-dose norepinephrine increased water absorption in both groups at two weeks; the change in flux for high-dose norepinephrine was greater in DEN versus controls (4.1 ± 1 vs 2.1 ± 0.6 μl/min/cm, P = 0.04). Net absorptive fluxes of Na+ and Cl− followed these trends. VIP did not alter absorption of water or electrolytes. Extrinsic denervation of the proximal colon causes a decrease in net colonic absorption and a transient, proabsorptive adrenergic hypersensitivity in colonic absorption of water and electrolytes. VIP does not have a net secretory effect in the proximal canine colon.