The conformation of prostaglandin F 2α (PGF 2α ) has been determined by x-ray diffraction techniques. Two independent conformers of PGF 2α , studied as the tris(hydroxymethyl)methylamine salt, are observed to adopt the familiar "hairpin" conformation with the α and ω chains aligned roughly parallel. The conformers differ in ring conformation and at the C(17)-C(18) bond, one adopting a C(9) envelope ring conformation and a trans geometry at the C(17)-C(18) bond, while the other adopts a C(8) envelope ring conformation and a novel gauche geometry about C(17)-C(18). Comparison of the conformation of PGF 2α with that of prostaglandin E 2 suggests a recognition mechanism which would permit PGF 2α and prostaglandin E receptors to distinguish between the two potent prostaglandins. The recognition model explains much of the binding data for the PGF 2α receptor in the corpus luteum and predicts the existence of an interesting PGF 2α analog.