Mast cells from Hsd11b1−/− mice have a phenotype consistent with relative glucocorticoid deficiency, including reduced expression of glucocorticoid-sensitive mast cell-specific carboxypeptidase A3, suggesting 11β-HSD1-mediated glucocorticoid amplification tonically suppresses mast cell responses. The gene discussed is CPA3; the disease is familial glucocorticoid deficiency.