Androgen-dependent (SC3) and -independent (CADO21) cloned cell lines were established from androgen-dependent mouse mammary tumor (Shionogi carcinoma 115). The effects of conditioned medium (CM) collected from SC3 and CADO21 cells on the anchorage-independent growth of SC3 cells in soft agar were studied. CM prepared from SC3 cells in the absence of testosterone was unable to stimulate the growth of SC3 cells, whereas CM prepared from SC3 cells in the presence of 10(-8) M testosterone stimulated the growth of SC3 cells in a concentration-dependent manner (21 colonies at 10% and 48 colonies at 20%) and this growth-stimulatory effect was not inhibited by 10(-6) M cyproterone acetate. CM prepared from CADO21 cells in the absence of testosterone was also able to stimulate the SC3 cell growth in a concentration-dependent manner (9 colonies at 10% and 19 colonies at 20%). These results suggest that the growth of androgen-dependent SC3 cells is stimulated by androgen-induced growth factor(s) produced from the same cells (autocrine mechanism) and is also regulated by autonomous growth factor(s) produced from androgen-independent cancer cells formed from the dependent cancer cells (paracrine mechanism). A suggested possible mechanism of the progression from androgen-dependent to -independent growth of cancer cells is also discussed.