Using histochemical and immunocytochemical methods the intramural neural tissue of the pancreas was investigated in non-diabetic and in alloxan-diabetic rats. It was demonstrated that the non-diabetic pancreas contains an average of 2.71 cells/mm3 tissue that react positive for activity of acetylcholinesterase and 2.38 cells/mm3 tissue that show monoamine oxidase activity. Both cholinergic and monoaminergic cells are found as solitary cells and in clusters of various sizes. All these cells are embedded in the exocrine tissue. Both histochemical methods revealed the presence of intra-insular fiber plexuses. Treatment with alloxan resulted in disappearance of intra-insular cholinergic and monoaminergic activity and also in a 68% reduction of the cholinergic cells and 54% of the monoaminergic cells in the diabetic pancreas. Application of immunocytochemical methods employing antibodies against norepinephrine and dopamine demonstrated the noradrenergic character of at least some of the monoaminergic cell groups. It is discussed how the present data and data from previous innervation studies provide evidence for an intramural ganglionic organization of the sympathetic innervation of the rat pancreas.