Mammary adenocarcinomas were induced by medroxyprogesterone acetate (MPA) in female BALBlc mice. From 5 primary tumors, 9 different sublines were established by s.c. transplantation into syngeneic female mice; these developed after a long latent period (4-12 months). Each subline was transplanted both into 4 mice treated with 40mg of MPA depot (s.c. contralaterally to the tumor inoculum) and into 4 non-treated mice. Of the 9 sublines, 6 proved to be hormonedependent (MPA-D) and 3 hormone-independent or autonomous (MPA-I). However, even the autonomous lines, when treated with MPA, showed a slight increase in growth. All MPA-D lines had a high content of ER (26254 fmoles/mg of protein), PR (63-710). PRL-R (44-74) and low or nondetectable EGF-R. Of the 3 MPA-I sublines that were studied, 2 showed a high content of ER (16-125), PR (27-708), PRL-R (19-70) and EGF-R (2965) while the other one had a low content of ER (0-36), PR (0-13), no EGF-R and moderate PRL-R (I 5-52). Spontaneous mammary tumors of BALBlc and C3H origin, which also showed an MPA-I pattern of tumor growth, had high levels of EGF-R. We postulate that MPA has a direct effect on mammary tumor cells in MPA-D lines and that the expression of EGF-R is correlated with an autonomous pattern of growth.