Two gamma-emitting estrogen analogues, (2R*,3S*)-1-[125I]iodo-2,3-bis(4-hydroxyphenyl)pentane ([125I]iodonorhexestrol) and (2R*,3S*)-1-[77Br]bromo-2,3-bis(4-hydroxyphenyl]pentane ([77Br]bromonorhexestrol), have been prepared by halide ion displacement on a labile trifluoromethanesulfonate derivative of a suitably protected precursor, followed by mild acid deprotection. Although halide displacement on a more stable tristrifluoromethanesulfonate derivative was successful, the basic conditions required for deprotection of this precursor resulted in destruction of the products by a base-induced spiroelimination reaction. In immature female rats, both of these halonorhexestrols demonstrated preferential uptake by the uterus that could be blocked selectively by coadministration of a large dose of unlabeled estradiol. In a double label comparison with 16 alpha-[125I]iodo-17 beta-estradiol the uterine uptake of [77Br]bromonorhexestrol was notably less selective. Stability studies in vitro and in vitro have indicated that both iodo- and bromonorhexestrol are quite labile, and this lability compromises the selectivity of their uptake by estrogen target tissues in vivo. p-Hydroxyphenethyl halides are known to be unusually prone to a base-catalyzed solvolysis, via cyclization of the phenolate to a spirocyclohexadienone intermediate. This unusual solvolytic mechanism may contribute to the lability of these halonorhexestrols in vivo.