The non-steroidal anti-oestrogen tamoxifen inhibits proliferation of the A549 human lung adenocarcinoma cell line (EC50 congruent to 10 nM) yet there was no evidence of oestrogen receptor expression as determined by ligand binding assay and northern blotting. 17-beta-Oestradiol had no effect on A549 cell proliferation (1 pM-1 microM) and moreover a 100-fold excess failed to reverse the effect of 10 nM tamoxifen as did a 100-fold excess of the steroidal anti-oestrogens ICI 164384 and ICI 182780. However, 4-hydroxytamoxifen which had no significant effect on A549 cell growth (1 pM-1 microM) completely antagonized the effect of 10 nM tamoxifen when used at a 100-fold excess. In the presence of oleic acid and stearic acid (10 microM) the growth inhibitory effect of tamoxifen in A549 cells was greatly enhanced, unlike effects mediated by the anti-oestrogen binding protein described in other cells where these fatty acids had no effect. These results indicate the presence of a unique and highly sensitive mechanism in A549 cells whereby concentrations of tamoxifen relevant to classical receptor binding can inhibit cell growth in the absence of the oestrogen receptor.