The modulatory effect of 1, 25 dihydroxyvitamin D3 (vit D) and 13 cis retinoic acid (retinoic acid) on the growth and differentiation of normal human pluripotent stem cell, erythroid, and myeloid progenitor cell growth was studied using semisolid methylcellulose clonal assay. Dose response curves showed that maximal increments of myeloid colony (CFU-C) growth (150%) occurred with vit D at 2 X 10 (-9)-2 X 10 (-8) M and with retinoic acid (184%) at 1 X 10 (-7) M. Vit D caused a 134% increase in macrophage colonies (CFU-M) and a decrease in granulocytic (CFU-G) and granulocyte-macrophage colonies (CFU-GM)(50% and 58%, respectively, as compared to the control). Retinoic acid did not alter the differentiation pattern of myeloid colonies (CFU-M, CFU-G, and CFU-GM). Vit D at 2 X 10 (-8) M had an inhibitory effect on BFU-E (62% growth of control) and did not affect CFU-mix growth. Retinoic acid at 10 (-7) M did not alter the growth of either BFU-E or of CFU-mix. Cellular differentiation studies in liquid suspension showed that vit D caused a 213% increase in monocyte-macrophages and a 56% and 26% decrease in immature and mature granulocytes, respectively. Retinoic acid caused a marked (79%) decrease in immature granulocytes whereas the percentage of mature granulocytes and monocyte-macrophages was not changed. Assessment of phagocytosis and killing of Candida albicans (CA) by cultured monocyte-macrophages and granulocytes exposed to vit D and retinoic acid demonstrated that treated cells had the same capability to phagocytose and kill CA as did untreated cells.