Vitamin D analogs have much potential in the treatment of certain cancers, psoriasis, rickets, and many other human disorders. Potentially medically useful analogs can be designed through structure-activity studies to yield compounds that retain the antiproliferative activity of calcitriol, but that exhibit diminished calcemic effects. New analogs containing a 23-oxa allylic type functionality have been prepared, exhibiting remarkable activity. Many of these compounds are more active antiproliferatively than the natural hormone calcitriol in vitro while requiring 50 times the concentration of calcitriol to reach the same calcemic levels in vivo. This desirable therapeutic index encourages further evaluation of these analogs as potential drug candidates.