Novel carborane-containing estrogen receptor (ER) modulators, carbamate and thiocarbamate derivatives 5 and 6, were designed and synthesized based upon the m-carborane bisphenol skeleton. Their activities were evaluated by competitive binding assay with recombinant human ERalpha, transcriptional activation assay and cell proliferation assay. All test compounds dose-dependently bound to human ERalpha and showed potent estrogenic activity. The binding affinities of thiocarbamates 6a and 6b are higher than those of the alkyl carbamates 5a-5d and are similar to that of the phenyl carbamate 5e. The binding affinity was well correlated with the acidity of the NH proton, indicating the existence of an interaction between the NH proton and amino acid residue(s) of the ERalpha ligand binding domain. The amino acid residue(s) interacting with the NH proton appears to be different from Asp351, which is known to play an important role in the expression of antiestrogenic activity. The side chain of the m-carborane bisphenol structure strictly controls the balance of estrogenic and antiestrogenic activities, and the (thio)carbamates can be classified as an agonist group.