We hypothesized that increasing the level of circulating serum estrogen would decrease the load at failure for the rabbit anterior cruciate ligament. We developed an animal model in which hormonal manipulations could be correlated with load at failure for the anterior cruciate ligament. Sixteen New Zealand White ovariectomized rabbits were matched and divided into two groups. The eight rabbits that were not treated with the estrogen supplement (Group O) and the eight that were treated with the supplement (Group E) were housed for 30 days. Serum estrogen levels were measured. The knees were stripped of all soft tissue, and the load at failure for the anterior cruciate ligament was measured in a materials testing machine with a displacement rate of 0.5 mm/sec. The load at failure for all 16 specimens in Group E (446 +/- 54 N) (mean +/- SD) was significantly reduced (p = 0.02) compared with that for the nine specimens in Group O (503 +/- 48 N). It is recognized that an increased number of anterior cruciate ligament injuries occurs in female athletes. Although the mechanism responsible for failure of the anterior cruciate ligament in women is yet to be defined, this experiment suggests that estrogen may alter ligament strength.