The aim of the present prospective controlled study was to examine the influence of 17 beta-estradiol and tibolone on tumor necrosis factor-alpha (TNF-alpha) levels in healthy women with surgical menopause. Forty-five surgically menopausal women were included in the study. Thirty women were randomized to receive tibolone 2.5 mg or 17 beta-estradiol 2 mg daily for 16 weeks. Fifteen surgically menopausal women who refused hormone therapy served as controls. Serum was collected from the subjects at baseline and at the end of the study for TNF-alpha assay. Neither tibolone nor 17 beta-estradiol showed a significant influence on TNF-alpha level at the end of 16 weeks in comparison with baseline. Although tibolone induced a trend toward decreased level of TNF-alpha (3.30 +/- 0.42 vs. 2.56 +/- 1.94 mu g/dl), this was non-significant. The slight increase observed in TNF-alpha level in the control group was also insignificant (3.60 +/- 1.20 vs. 4.10 +/- 0.70 mu g/dl). Overall, these results demonstrate no significant effects of either tibolone or 17 beta-estradiol on circulating TNF-alpha level in surgically menopausal women. However, the significant difference achieved between the tibolone and control group after treatment is promising and needs to be investigated in trials with longer treatment periods.