ABSTRACT The purpose of this paper is to report on the in vivo effect of different doses of cis- and trans-clomiphene on the RNA and protein synthesis in the ovary, liver, adrenal gland and uterus of newborn guinea pigs. After the sc injection of either isomer the biochemical parameters were determined at different time intervals. Both isomers induced an increase of the RNA- and protein-synthesizing activity in the uterus, but failed to do so in the ovary, liver and adrenal gland. According to data reported here and also by other investigators it may be assumed that the lack of ovarian response to the treatment with cis- or trans-clomiphene is primarily due to the functional immaturity of the female hypothalamus and/or pituitary during the neonatal period. Both isomers failed to modify the pattern of gonadotrophin release, as shown by the constancy of the ovarian RNA and protein synthesis after the administration of either of the isomers. In the uterus, both cis- and trans-clomiphene strikingly imitated the biochemical stimulation produced by natural oestrogens. In contrast to oestradiol-17β, both clomiphene isomers showed a later onset and longer duration of the oestrogenic activity. The first increase of the amino acid incorporation into uterine proteins was noted after 5 hours in the cis-clomiphene treated group and after 8 hours in the trans-clomiphene treated animals as compared to 1 hour when oestradiol-17β was used. This difference seems to be due to a delayed transfer of the cytoplasmic oestradiol receptor to the nucleus after the injection of cis- or trans-clomiphene. As compared to oestradiol-treated animals, the clomiphene injection provoked a prolonged elevation of the uterine protein-synthesizing activity, most likely reflecting an effect of the enterohepatic recirculation of both isomers.