Steroid receptors were measured in a series of 30 operable canine mammary gland tumors; both cytoplasmic estrogen (ERc) and progesterone (PgRc) receptor mean concentrations were very low with respect to the mean levels found in humans. Therefore a study was designed to modulate receptor levels by administration of Tamoxifen and Etretinate, either alone or in combination. Forty dogs with resectable, histologically documented mammary gland tumors were subdivided into the following treatment groups: a. Etretinate (1 mg/kg/d) p.o. for 7 days followed by Tamoxifen (0.7 mg/kg/d) p.o. for 7 days; b. Tamoxifen (0.7 mg/kg/d) p.o. for 14 days; c. Etretinate (1 mg/kg/d) p.o. for 14 days; d. 14 days placebo, and cytoplasmic ERc and PgRc and nuclear ER (ERn) were measured before and after the treatment. An increase of ERc and ERn was observed after administration of Tamoxifen, while an increase of ERc only was seen after treatment with Etretinate. We conclude that canine mammary tumors are indeed hormone sensitive despite their very low receptor concentrations and a suitable treatment can in fact modulate receptor levels. However, further studies are needed better to define the optimal treatment regimen in order to achieve maximal steroid receptor induction.