Soy diets suppress the development of neuropathic pain behavior in rats undergoing partial sciatic nerve ligation (PSL) injury. Phytoestrogens, plant isoflavones and lignans, abundantly found in soy products, have powerful estrogenic properties. Because, in some preparations, steroid estrogens were found to exert antinociception, we examined whether the analgesic effect of dietary soy is mediated by phytoestrogens. Male Wistar rats were fed five different diets containing 8-180 microg of phytoestrogens per gram. These diets were administered 2 wk before and 2 wk after PSL injury. Levels of tactile allodynia and mechanical and heat hyperalgesia of these rats were determined on Days 3, 8, and 14 after PSL injury. Plasma levels of two major phytoestrogens (genistein and daidzein) and two daidzein metabolites (equol and dihydrodaidzein) were assessed on Day 14 postoperatively. We found that the plasma concentration of these phytoestrogens and the levels of allodynia and hyperalgesia varied highly among dietary groups. Average plasma concentrations of phytoestrogens were associated with reduced levels of tactile allodynia and mechanical hyperalgesia, but not with reduced heat allodynia. Low and high plasma phytoestrogen levels were not analgesic in these tests. This report is the first to show that, at certain plasma concentrations, phytoestrogens reduce neuropathic pain in rats. Dietary soy suppresses neuropathic pain in rats after partial sciatic nerve ligation. Some of the pain-suppression properties of soy can be attributed to phytoestrogens, isoflavones abundantly found in soy products. Average, but not low or high, plasma levels of phytoestrogens are associated with analgesia.