Impaired fluid and electrolyte transport in the intestine is a well-recognized characteristic of radiation-induced pathologies in the gastrointestinal tract. The aim of this study was to investigate the responsiveness of the epithelium of the colon of the rat to electrical and pharmacological (serotonin, carbachol) stimulation concomitantly with in vivo assessment of the absorptive capacity of the colon at 1, 3, 5 and 7 days after 3.8 Gy whole-body exposure to neutrons. The responsiveness of rat colon in vitro to electrical stimulation and the number of mast cells were measured to examine the role of neuroimmune networks in radiation-induced dysfunction. Animals showed an impaired capacity of the colon to absorb water and sodium from 3 to 5 days after irradiation together with decreased responsiveness to electrical and pharmacological stimulation. The time course of decreased responsiveness to neural stimulation was similar to that of impaired absorption observed in vivo, but it was not correlated with variations in mast cell numbers. Histological (mast cells) and biochemical analyses (myeloperoxidase and NO synthase activities) did not find evidence of a marked infiltration and/or activation of inflammatory cells. Thus the impaired absorptive capacity of the colon observed after irradiation occurs concomitantly with decreased neural influence, and is possibly related to reduced epithelial functional capacity but not to decreased mast cell numbers.