SummaryThis study describes the innervation of uterine fibroids in a retrospective survey of archived material. A total of 24 uteri containing fibroids were identified; four nulliparous uteri with single large fundal fibroids (200 – 320 g) and 20 multiparous uteri with one, or more, fibroids (80 – 230 g). Tissue blocks from the uterine isthmus and the fibroids, were identified, sectioned and stained for nerves with anti-S100 using a standard immunohistochemical regimen. Normal uterine innervation includes concentrations of nerves in the subserosal layer and at the endometrial-myometrial interface with sparse neurovascular bundles distributed throughout the myometrial stroma. Nulliparous uteri with single large fibroids demonstrated relatively normal patterns of innervation with nerves distributed throughout the stroma of the fibroid. In multiparous uteri with fibroids, there were no nerves detectable in the substance of the fibroids. Increased numbers of nerve fibres were observed in the pseudo-capsule of some fibroids and may reflect compression of normal myometrial tissue and their contained nerves, or, a minor degree of nerve fibre proliferation. This study demonstrates that fibroids in multiparous uteri do not contain nerves. Single, large nulliparous fibroids situated at the uterine fundus appear to contain relatively normal patterns of innervation.