Vitamin D3 is a new therapeutic aim for psoriasis. Hyperproliferation and over-secretion of IL-8 of keratinocytes are the characteristic features for psoriasis. The purpose of present study is to determine whether vitamine D3 and the analogues could be effective in inhibiting the proliferation and IL-8 secretion of normal human epidermal keratinocytes. Cell proliferation was measured colorimetrically by the MTS assay. IL-8 secretion was measured with ELISA. Cell proliferation was inhibited in the presence of vitamine D3. 22-oxacalcitriol inhibited proliferation stronger than 1,25-dihydroxyvitamin D3 or 1,24R(OH)2D3. Fifty percent inhibition by 22-oxacalcitriol was observed at 1 10 - 9 M for 48 hours. IL-8 level secreted from keratinocytes was augmented by TNF-α, or synergistically by TNF-α and IFN-γ. Vitamin D3 inhibited cytokine-stimulated IL-8 production dose dependently without inhibition of cell proliferation. Fifty percent inhibition of IL-8 secretion was observed between 1 10 - 8 and 1 10 - 7 M in 22-oxacalcitriol and at 1 10 - 7 M in 1,25-dihydroxyvitamin D3. In conclusion, 1,25-dihydroxyvitamin D3 and 22-oxacalcitriol inhibit the keratinocyte proliferation directly and inhibit one of the reactions to cytokines for keratinocytes.