This study was undertaken to assess a possible role for cholinergic agents in the regulation of intestinal immunoglobulin A secretion. Intestinal loops, constructed in anesthetized rats, were perf used with phosphate buffered normal saline. Immunoglobulin A concentrations were measured by radioimmunoassay. When compared with the effect of normal saline in the same rats, intravenous injection of pilocarpine, 10 mg/kg, increased immunoglobulin A concentrations in perf usates from ilea] loops (p < 0.001). Qualitatively similar results were obtained with muscarine and bethanechol, from jejunal and colonic loops, and from unanesthetized rats. Immunoglobulin A concentrations increased four- to eightf old during maximal cholinergic stimulation. Atropine, 250 μg intravenously, completely blocked the effect of pilocarpine on immunoglobulin A secretion (p < 0.005), and also inhibited basal intestinal immunoglobulin A secretion for 40 min after injection. As determined on 10%-40% sucrose density gradients, much of the immunoglobulin A secreted after cholinergic stimulation sedimented in the 11S range. These data indicate that intestinal secretion of immunoglobulin A is stimulated by the muscarinic effect of cholinergic agonists, and suggest that basal secretion of immunoglobulin A may be influenced by the parasympathetic nervous system.