Despite over 40 years of study, the pathogenetic mechanisms of Trichomonas vaginalis are just starting to be elucidated. We have recently reported that T. vaginalis produces a virulence factor, cell-detaching factor (CDF), that likely causes the cell sloughing seen in clinical disease. This 200-kDa glycoprotein is acid and heat labile and correlates with clinical symptoms. We applied a McCoy cell culture system to study the effects of various concentrations of beta-estradiol (10(-6) to 10(-10) M) on T. vaginalis growth and CDF production. T. vaginalis growth was unaffected by the different concentrations of beta-estradiol studied, in comparison with the growth of control cultures without beta-estradiol. However, beta-estradiol significantly diminished the activity of CDF at all concentrations and did so most profoundly at 10(-7) and 10(-8) M (P less than 0.0001). This suggests that the symptoms of T. vaginalis infection may be influenced by the vaginal concentration of estrogens, and further studies of the interactions between T. vaginalis and estrogens are warranted.