The ability of an aqueous extract prepared from dried leaves of the South American shrub Solanum glaucophyllum to interact with a chick intestinal receptor system highly specific for the biologically active form of vitamin D, 1alpha, 25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3), was monitored under both in vivo and in vitro conditions. The pretreatment of chicks with the S. glaucophyllum extract reduced the amount of subsequently administered radioactive 1alpha, 25-dihydroxyvitamin D3 localized in the intestinal chromatin fraction by 90% when compared with vitamin D-deficient controls. In addition, the active principle in the aqueous extract was found to compete effectively with 1alpha, 25-(OH)2D3 in a reconstituted intestinal receptor system in vitro. The plant factor(s) was found to be as effective as 1alpha, 25-(OH)2D3 in decreasing the renal 25-hydroxycholecalciferol-1alpha hydroxylase activity levels when administered to vitamin D-deficient chicks. By means of the in vitro intestinal receptor assay, it was possible to estimate that there are approximately 10 to 60 mg of the biologically active material in one kilogram of dries S. glaucophyllum leaves. These data indicate that the plant factor(s) may be a structural analog of 1alpha, 25-(OH)2D3 and suggest the feasibility of its isolation.