Lipopolysaccharide (LPS) is known to raise the concentration of the circulating stress hormones such as ACTH, corticosterone and β-endorphin. This effect of endotoxin is mediated by different immune system-released hormone-like factors (e.g. interleukins, tumor necrosis factor etc.). Gamma-ray irradiation of LPS alters its biological properties and results in a radiodetoxified LPS preparation with numerous beneficial effects and decreased toxicity. In this study we compared the neuroendocrine effects of a commercial LPS and our native and radiodetoxified LPS preparations in rats. Plasma ACTH, corticosterone and β-endorphin levels were measured by specific radioimmunoassays 120 min after intraperitoneal LPS administration. Control animals were injected with saline. Results show a dramatic increase in all hormones after administration of commercial and our native LPS preparation. Hormone levels in saline-injected controls and radiodetoxified LPS-treated rats did not rise significantly. These results suggest that radio-detoxification disintegrated that part of the LPS molecule complex which is responsible for toxicity including an enhanced production of cytokines, which trigger the hypothalamo-pituitary-adrenal axis.