Many individuals are chronically infected or parasitically colonized with mycoplasmas in their respiratory or urogenital tracts without apparent clinical significance, However, prolonged close interaction between prokaryotic agents and eukaryotic host cells may gradually and significantly alter normal biological or physiological properties of infected hosts. Steroid hormones are associated with rates of cancer fort-nation in human, The purpose of this study is to establish a sensitive reporting system to examine whether mycoplasmal infections affect biological responses to steroid hormones in mammalian cells. We established pMTV-CAT stably transfected cell lines to test the effect of mycoplasmal lipid-associated membrane proteins (LAMPs). Results showed that LAMPs (1 mug/ml) from seven different species of human mycoplasmas-M. penetrans, M. fermentans, M. genitalium, M. salivarium, M, pneumoniae, M. orale, and M, hominis - had an inhibitory effect on androgen receptor (AR) response to Sa-dihydrotestosterone (DHT) in the E82 transfectants. The inhibitory effect of mycoplasmal LAMPs appeared to be dose dependent. LAMPs from M, penetrans, M. genitalium, M. salivarium, M. pneumoniae, and M. orale also had an inhibitory effect on glucocorticoid receptor (GR) response to hormone dexamethasone (Dex) in TSU transfectants. In contrast, LAMPs from M. fermentans and M. hominis showed a stimulatory effect on the GR response to Dex in these TSU cells. The results suggest that colonization or chronic infection by mycoplasmas may significantly affect the responses of mammalian host cells to various steroid hormones, potentially affecting rates of cancer formation.