The aim of this study was to characterize in vivo rat colonic motor activity in normal and inflamed states and determine its neural regulation. Circular muscle contractions were recorded by surgically implanted strain-gauge transducers. The rat colon exhibited predominantly giant migrating contractions (GMCs) whose frequency decreased distally. Only a small percentage of these GMCs propagated in the distal direction; the rest occurred randomly. Phasic contractions were present, but their amplitude was very small compared with that of GMCs. Inflammation induced by oral administration of dextran sodium sulfate suppressed the frequency of GMCs in the proximal and middle but not in the distal colon. Frequency of GMCs was suppressed by intraperitoneally administered atropine and 4-diphenylacetoxy-N-methyl-piperidine methiodide and was enhanced by N^w-nitro-L-arginine methyl ester. Serotonin, tachykinin, and calcitonin gene-related peptide receptor or receptor subtype antagonists as well as guanethidine and suramin had no significant effect on the frequency of GMCs. Verapamil transiently suppressed the GMCs. In conclusion, unlike the canine and human colons, the rat colon exhibits frequent GMCs and their frequency is suppressed in inflammation. In vivo GMCs are stimulated by neural release of acetylcholine that acts on M₃ receptors. Constitutive release of nitric oxide may partially suppress their frequency.