Interleukin (IL)-19 and IL-24 belong to the IL-20 subfamily, and are involved in host defence against bacteria and fungi, tissue remodelling and wound healing. Nevertheless, no previous studies have explored their expression in Mexican mestizo patients with inflammatory bowel disease (IBD). The aim of the study was to characterize and to enumerate peripheral and tissue IL-19- and IL-24-producing cells, as well as gene expression in patients with IBD with regard to its clinical activity. We studied a total of 77 patients with ulcerative colitis (UC), 36 Crohn's disease (CD) and 33 patients as control group (without endoscopic evidence of intestinal inflammation). Gene expression was measured by real-time–polymerase chain reaction (RT–PCR). Protein expression was detected in biopsies by immunohistochemistry and in freshly isolated peripheral blood mononuclear cells by flow cytometry. IL-19 and IL-24 gene expression was elevated significantly in patients with active IBD versus the inactive disease and non-inflammatory control groups (P < 0·05). However, IL-19- and IL-24-producing cells were only increased in active CD versus active UC and non-inflammatory tissues (P < 0·05). IL-19 was produced conspicuously by circulating B cells and monocytes in patients with inactive disease (P < 0·05). Conversely, IL-24 was noticeably synthesized by peripheral B cells, CD4+ T cells, CD8+ T cells and monocytes in patients with active disease. In conclusion, IL-19- and IL-24-producing cells in active CD patients were increased compared with active UC and non-inflammatory tissues. These cytokines could significantly shape and differentiate inflammatory process, severity and tolerance loss between UC and CD pathophysiology.