We performed a case-control study on the influence of oophorectomy on the development of degenerative spondylolisthesis, including a clinical review and determination of serum oestradiol levels. We also compared the radiological appearance of the lumbar spine at L4/5 in patients with and without spondylolisthesis and with and without oophorectomy. Oophorectomy was a risk factor for degenerative spondylolisthesis with an odds ratio of 7.5 (95% confidence interval, 1.6 to 46). The incidence of degenerative spondylolisthesis in 69 oophorectomised patients was about three times higher than in 69 non-oophorectomised matched control subjects. There was also a difference in spinal variation between oophorectomised and non-oophorectomised patients with spondylolisthesis. A high incidence of sagittal-plane orientation of the L4/5 facet and an increase in pedicle-facet angle were seen in both groups and are typical radiological features of this disease. An increase in lumbosacral angle and in disc-space narrowing was seen only in the non-oophorectomised patients with this condition. Our results suggest that the abrupt decrease in oestradiol level caused by oophorectomy may be a predisposing factor in degenerative spondylolisthesis at L4/5.