We have cloned and sequenced 4.5 kilobases (Kb) of cDNA encoding the chicken progesterone receptor. The complete cDNA contains an open reading frame of 2361 nucleotides in length and encodes a polypeptide of 787 amino acids with a mol wt of 85.9 K. At least four mRNA species have been detected in chick oviduct cells. Direct sequencing of variant cDNAs has suggested that two of the mRNAs (4.5 Kb and 3.6 Kb) differ only in the length of their 3'-untranslated regions. A third mRNA (1.8 Kb) produces a truncated polypeptide which encodes the immunoreactive NH2 terminal sequence of the receptor but lacks the hormone binding regional and half of the DNA-binding domain. The polypeptide expressed from the receptor cDNA in progesterone receptor negative Cos M-6 cells is indistinguishable from oviduct progesterone receptor in terms of hormone binding and antibody reactivity. Furthermore, the cloned receptor is capable of activating transcription of a target gene. This activation is progesterone dependent (with half-maximal stimulation at approximately 3.3 x 10(-10) M) and specific for the target gene.