Although substance P has been demonstrated in the nonhuman ovary, it has not previously been identified in normal human ovarian tissue. We examined ovarian surgical specimens from 30 women for the presence of immunoreactive substance P. With the use of a specific radioimmunoassay, immunoreactive substance P was identified in these ovarian extracts. The geometric mean of the immunoreactive substance P concentration was 0.55 pg/mg wet weight (95% confidence limits 0.04 and 6.15). Thecal and stromal concentrations of immunoreactive substance P were greater than those in the corpora lutea and tunica albuginea. Large follicles had a lower concentration of immunoreactive substance P than did small follicles. We conclude that the neuropeptide substance P is present in some normal human ovaries and may be a modulator of ovarian function.