The complexes 17 alpha-[(C=CC5H4)M(CO)(3)]-estradiol, M = Re (17) and Mn (18), were prepared either by reaction of (LiC=CC5H4)M(CO)(3) with estrone or by the Pd-catalyzed coupling reaction of 17 alpha-ethynylestradiol with (C5H4I)Re(CO)(3). Analogously, 11 beta-(chloromethyl)-17 alpha-[(C=CC5H4)Re(CO)3]-estradiol (19) was prepared from (LiC=CC5H4)Re(CO)(3) and 11 beta-(chloromethyl)estrone. 19 was characterized by X-ray crystallography : space group P2(1)2(1)2(1) (orthorhombic), a = 8.189(2) Angstrom, b = 15.247(6) Angstrom, c = 20.549(9) Angstrom, V = 2566(2) Angstrom(3), Z = 4. The complexes 17 alpha-[(CH2C5H4)M(CO)(3)]-estradiol, M = Re (22) and Mn (23), were prepared by reaction of (C5H4Li)M(CO)(3) with spiro[oxirane-2,17 beta’-estra-1,3,5(10)-trien-3-ol]. The relative binding affinities (RBA’s) of these complexes for the estradiol-specific receptor are compared to that of the natural hormone. The low RBA values for 22 (0.8%) and 23 (2.5%) are rationalized on the basis of the flexible character of their bulky 17 alpha substituents; in contrast, the alkynyl derivatives 17 and 18 adopt conformations in which the organometallic fragments lie beneath the steroidal D ring, as in the X-ray structure of 19, and their relative binding affinities are reasonably good (16% and 15%, respectively). It is proposed that the extraordinarily high RBA for 19 (172% at 25 degrees C) can be accounted for in terms of an interaction of the 11 beta-chloromethyl substituent with a Lewis acid proximate to the receptor binding site. Some modeling studies of the dimeric receptor are in agreement with this hypothesis. The lipophilicities of these complexes have been estimated by measuring their partition coefficients between octanol and water, and these P-o/w coefficients are related to the degree of nonspecific binding to low affinity sites. The potential utility of isotopically labeled steroidal rhenium complexes both as imaging agents and in radiotherapy is discussed.