Cyclic vomiting syndrome is characterized by sudden episodes of vomiting and abdominal pain. It occurs primarily in children, is exacerbated by stress, and is often considered a migraine equivalent. Migraines have been linked to mast cells, which are often found close to neurons where they are activated by neuropeptides. We investigated the ultrastructural appearance of rat ileal brush border and mast cells following acute stress by immobilization. The effect of sulfated proteoglycans heparin and chondroitin sulfate was also tested on mast cell histamine secretion. Ileal brush border appeared intact in control animals, but was shorter and exhibited intercellular gaps after 30 min of acute immobilization stress. Mast cell activation in control rats was minimal, while stress induced obvious signs of activation as judged from disappearance of secretory granule electron dense contents. However, these intragranular changes were not accompanied by typical degranulation through exocytosis. Treatment of purified homogeneic rat peritoneal mast cells with 10(-4) M heparin or chondroitin sulfate 30 min prior to stimulation with 0.5 microg/ml compound 48/80 decreased histamine release by over 70% and 50% (P < 0.05), respectively. These results suggest the possible usefulness of chondroitin sulfate in conditions such as cyclic vomiting syndrome.