In addition to its well defined role as a key regulator of calcium and bone metabolism, 1,25-dihydroxyvitamin D 3 (calcitriol) has been established as a potent modulator of immune cell function. Still, because of the hypercalcemic toxicity occurring after systemic application of the parent compound, its clinical application as an immunosuppressant has been hampered. Recently, we described 22-ene-25-oxa-vitamin D (ZK156979) as a representative of a novel class of low calcemic vitamin D analogs with well preserved immunosuppressive activity in vitro. Here, in vivo colitis was induced by applying a rectal enema of 2,4,6-trinitrobenzene sulfonic acid (TNBS) to male BALB/c mice, and calcitriol (0.2 g/kg) or ZK156979 (0