We have previously shown that estrogen administration to male Xenopus laevis results in the posttranscriptional suppression of serum albumin mRNA concurrent with the transcriptional activation of the genes for the yolk protein precursor vitellogenin. To determine whether the posttranscriptional regulation of albumin gene expression is mediated through a mechanism involving the high affinity estrogen receptor protein or through a receptor-independent mechanism involving a middle affinity cytoplasmic estrogen-binding protein we examined the effects of the competitive estrogen receptor antagonist 4-hydroxytamoxifen. Administration of 4-hydroxytamoxifen 24 h before estradiol completely blocked both the suppression of albumin mRNA and the transcriptional activation of the vitellogenin genes. Albumin gene transcription remained constitutive under all treatment regimens. Competitive binding experiments demonstrated that 4-hydroxytamoxifen has an affinity for the estrogen receptor similar to that of estradiol. However, 4-hydroxytamoxifen displays little or no interaction with the middle affinity cytoplasmic estrogen-binding protein. These data indicate that the estrogen receptor occupies a key role in the posttranscriptional regulation of albumin mRNA.