The changes induced in the relative concentrations of the different species of RNA (messenger, ribosomal, transfer and heterogenous) which regulate the metabolic behavior of tissues were studied in the endometrium of normal women and in women wearing a progesterone T IUD for 6-12 months. It was observed that the intrauterine release of progesterone is accompanied by a significant decrease in the content of total RNA (from 78 +or- 8.4 to 64 +or- 6.7 mcg/mg of protein) and in the RNA/DNA ratio (from 0.85 +or- 0.10 to 0.73 +or- 0.08). Although the protein decreased significantly (from 102 +or- 11 to 82 +or- 14 mg/g wet wt.), the DNA content and the Prot/DNA ratio were not altered. Using the affinity chromatography technique in poly(u)Sepharose it was found that the relative concentrations of RNA types were in general drastically modified: mRNA and rRNA decreased (from 2.6 +or- 0.31 to 1.28 +or- 0.15 and from 65.5 +or- 8.0 to 54.8 +or- 6.7 mcg/mg of protein respectively). tRNA content was increased (from 6.2 +or- 0.9 to 11.0 +or- 1.3) while hRNA was unchanged. The probable inhibitory effects of these changes in relation to the normal hormonal stimulation of the human endometrium, as a possible explanation of the mechanism of action of this device, are discussed.