Cloned cell lines derived from the androgen-responsive Shionogi 115 mouse mammary carcinoma, when cultured in the presence of 3.5 X 10(-8) M testosterone, retain their responsiveness to testosterone and 5alpha-dihydrotestosterone and exhibit fibroblast-like morphology; their growth is poorly regulated by cell density. Dexamethasone at 10(-8) M inhibits proliferation of these cells by 30% but stimulates them by 235% at 10(-6) M in the temporary absence of testosterone. Cell growth is little affected by serum concentration. When cultured for 3 to 4 weeks in testosterone-free medium, however, the cells lose their androgen responsiveness and retain the inhibitory but not the stimulatory response to dexamethasone. They also show an increased sensitivity to serum and increased density regulation and change to an epithelial morphology. It is suggested that the loss of sensitivity to androgens, which does not result from absence of androgen receptor, is related in a complex way to the increased sensitivities to serum and density regulation.