OBJECTIVE: The cause of vulvar vestibulitis syndrome is unknown. To determine a possible role for defective immune regulation in this chronic condition, proinflammatory and anti-inflammatory immune responses to the 70-kd heat shock protein and to lipopolysaccharide were compared in women with and without vulvar vestibulitis syndrome. STUDY DESIGN: Whole blood cultures from 62 women with vulvar vestibulitis syndrome and 48 control subjects were incubated in the presence or absence of 5 microg/mL human recombinant 70-kd heat shock protein or 0.1 ng/mL lipopolysaccharide for 18 hours. The culture supernatants were then assayed for interleukin-1 beta and interleukin-1 receptor antagonist by enzyme-linked immunosorbent assay. RESULTS: Median levels of interleukin-1 beta were higher in response to heat shock protein in cultures from patients with vulvar vestibulitis syndrome (median, 1.07 ng/mL) as opposed to control subjects (median, 0.40 ng/mL; P =.006). Conversely, levels of interleukin-1 receptor antagonist were higher in response to heat shock protein in control subjects (median, 39.21 ng/mL) than in patients (median, 29.25 ng/mL; P =.009).In response to lipopolysaccharide, median levels of interleukin-1 beta were similar in patients (1.00 ng/mL) and control subjects (1.15 ng/mL); median interleukin-1 receptor antagonist concentrations were higher in control subjects (70.0 ng/mL) than in patients (44.3 ng/mL; P <.0001). The ratio of interleukin-1 receptor antagonist to interleukin-1 beta was higher in control subjects than in women with vulvar vestibulitis syndrome in response to both heat shock protein (P =.0002) and lipopolysaccharide (P =.01). In uninduced cultures, interleukin-1 receptor antagonist levels were also higher in control subjects (median, 1.60 ng/mL) than in patients with vulvar vestibulitis syndrome (median, 0.62 ng/mL; P <.0001). CONCLUSION: A relative inability to down-regulate proinflammatory interleukin-1 beta activity by interleukin-1 receptor antagonist may contribute to the pathophysiologic features of vulvar vestibulitis syndrome.