TNF-α, a polypeptide secreted by macrophages has been shown to have a regulatory effect on ovarian function by attenuating the differentiation of granulosa cells through neutralization of follicle stimulating hormone (FSH) and decreasing leutinizing hormone stimulated progesterone production. TNF-α in women with endometriosis, may cause luteolysis and cytotoxicity against spermatozoa. Potential relationships between in vivo levels of TNF-α and its effect on in vitro fertilization (IVF) outcome remains to be elucidated. Levels of TNF-α were measured by RIA in serum of 28 IVF patients on day 3 of their menstrual cycle. Ten patients undergoing IVF achieved pregnancy and eighteen patients did not. Endometriosis was found in six patients who did not become pregnant versus one patient who achieved pregnancy. TNF-α levels were greater in patients who did not achieve pregnancy 2.80+/-0.67 pg/ml versus patients who achieved pregnancy 1.26 +/- 0.21 pg/ml (p<.05). Furthermore TNF-α levels were highest in women with =<3 recurrent abortions. In 3 of 5 (60%) patients, levels of TNF-α greater than 2.56 pg/ml had a cancellation of their IVF cycle secondary to poor response to gondatropins. TNF-α levels did not correlate with day 3 estradiol or number of atretic oocytes subsequently retrieved. In patients with endometriosis TNF-α levels 0.86+/-0.46 were not significantly elevated compared to levels in patients who achieved pregnancy. We conclude that elevated levels of TNF-α have a detrimental effect on IVF outcome; high levels may also play a role in the pathogenesis of recurrent abortions. TNF-α can potentially be used as a tool in predicting IVF success and possible future abortion.