The secosteroid 1 alpha, 25-dihydroxyvitamin D3 (calcitriol) and retinoic acid are the major biologically active metabolites of vitamins D and A, respectively. Their antitumor activity has been observed in several cancer cells in vitro apart from lung cancer cells. The purpose of this study was to examine the possible effects of the agents on lung cancer cell lines. The responses of five lung cancer cell lines to calcitriol or all-transretinoic acid (RA) were assessed by a colorimetric MTT assay. Calcitriol inhibited growth in one of the tested cell lines, ie EBC-1 squamous cell carcinoma, dose dependently. RA also exhibited the same effect in EBC-1 cells. However neither agent affected the growth of other lung cancer cell lines. Subsequently we examined the mRNA expression of vitamin D receptor (VDR) and retinoic acid receptor (RAR alpha) in these lung cancer cells by quantitative RT-PCR. EBC-1 cells expressed high levels of mRNA for both VDR and RAR alpha, while other cell lines expressed much lower mRNA levels for the receptors. These data suggest that the growth inhibitory effects of the vitamins are associated with mRNA expression for VDR and RAR alpha.