Clinical and experimental evidence suggests a role for estrogen in the natural history of desmoid tumors (DT). Antiestrogen (tamoxifen) has been used empirically in some patients with significant tumor regression. To further investigate the mechanism of hormonal influence on desmoid tumors we initially characterized the cytosol estrogen receptor (ER) and antiestrogen binding sites (AEBS) in microsomal fractions of 15 cases of DT. Biopsy specimens were obtained from nine female and six male patients. ER assay was determined in cytosol (105,000 g) and the AEBS was detected in the microsomal fraction (7000 g for 20 min) by a DCC assay technique. ER was present in 33% of DT assayed (5/15), with equal incidence in males and females. Receptor content in female patients was higher than in male patients (26.52 +/- 16 vs 10.82 +/- 8.32 fmol/mg protein). Dissociation constant (Kd) range (0.44-3.97 nM) was well within the values seen in other estrogen target tissues. The AEBS were detected in 79% of the cases. The mean binding value was 236.7 +/- 170.2 fmol/mg protein. Kd values were between 0.39 and 5.97 nM. ER settled predominantly in the 4S region and AEBS settled in the 5-5.5S region in a 5-20% sucrose gradient. AEBS was detected in seven patients with negative ER. No correlation between ER and AEBS contents was observed. Competition studies revealed minimal binding with either DEX, DHT, R5020, and R1881, but partial binding with tamoxifen in cytosol and estradiol in microsomal fractions. ER and AEBS assays may be of prognostic significance in the natural history of these tumors.