Concentration of radioiodide in the cells of the luminal epithelium of the ovariectomized rat after a single injection of progesterone was abolished by 300 μg cycloheximide/100 g body weight given with or 4 h after the progesterone. Actinomycin D at 32 or 80 μ/100 g body weight given with the progesterone did not inhibit the development of the iodide concentrating mechanism. Oestradiol given 16 h before or 2 h after progesterone inhibited the iodide response in a dose-dependent manner. The incorporation of [3H]uridine into histologically fixed material was significantly increased in all tissues of the uterus 1 h after progesterone. The incorporation of [3H]lysine into histologically fixed material was increased significantly in luminal epithelium at 3 h and in all uterine tissues at 7 and 24 h. These findings are consistent with the view that gene transcription may be stimulated by progesterone, resulting in the synthesis of proteins in the different tissues of the uterus. In the luminal epithelium however, progesterone may also stimulate protein synthesis and the development of the iodide response in the absence of gene transcription.