Earlier reports of oestrogen receptor binding to DNA indicated that a protein which does not bind oestrogen might be involved in the conversion of the 4S oestradiol receptor to the 5S form but no direct evidence for the existence of this protein was presented. This receptor transformation or activation step is thought to be a requirement for events in the nucleus. We considered it likely that such a protein might be similar to the cytoplasmic proteins which stimulate eukaryotic RNA polymerases. These are basic proteins which are not adsorbed to DEAE cellulose and have a sedimentation coefficient of approximately 3S. To examine this possibility, we fractionated unlabelled uterine cytosol by DEAE-cellulose chromatography. Unlabelled cytosol was used to avoid the possibility that such a factor might be retained on the column as a component of the receptor--oestradiol complex. Here we present evidence of a protein present in uterine cytosol which forms a complex with the 4S form of the oestrogen receptor to produce a 5S-activated form. This activated form binds to uterine nuclei, DNA-cellulose and native calf thymus DNA. The cytosol protein, which we call receptor activation factor, does not bind oestradiol, has a sedimentation coefficient of approximately 3S and does not bind to DEAE-cellulose.