IL-5, known to be produced by T lymphocytes and eosinophils, is a key regulator of intestinal diseases such as parasitosis or eosinophilic gastroenteritis. Here we examined if mast cells contribute to the IL-5 production in human intestinal mucosa. The number of IL-5-positive lamina propria cells was substantially higher in patients with intestinal inflammatory diseases (5.3 +/- 4.6%, n = 17) compared to healthy controls (0.5 +/- 0.9%, n = 8, p < 0.01). In patients, the IL-5-positive cells were eosinophils (70 +/- 13%) and mast cells (29 +/- 14%), whereas in controls all IL-5-positive cells were eosinophils. IL-5-positive T cells were not detected, likely because they do not store IL-5. In vitro studies with isolated human intestinal mast cells and eosinophils showed that mast cells do not produce IL-5 constitutively, but release high amounts of IL-5 (315 +/- 115 pg/10(6) cells) following IgE receptor cross-linking, compared to activated eosinophils (24 +/- 5 pg/10(6) cells). Inhibitor studies suggest a regulation of IL-5 production at the transcriptional level. In conclusion our data demonstrate that activated mast cells are a potent source of IL-5 in the human intestinal mucosa.