Lipoic acid is a lipophilic antioxidant that participates in many enzymatic reactions and is used clinically to treat mushroom poisoning and metal toxicity. In this report the protective effect of lipoic acid (oxidized form) against radiation injury to hematopoietic tissues in mice was assessed by the endogenous and exogenous spleen colony assays and survival (LD50/30) assay. Intraperitoneal administration of lipoic acid at a nonlethal concentration of 200 mg/kg body wt, 30 min before irradiation increased the LD50/30 from 8.67 to 10.93 Gy in male CD2F1 mice. Following a 9-Gy irradiation, the yield of endogenous spleen colony-forming units in mice treated with saline and lipoic acid was 0.75 +/- 0.5 and 8.9 +/- 1.6, respectively. Using the exogenous spleen colony assay, lipoic acid treatment increased the D0 from 0.81 +/- 0.01 to 1.09 +/- 0.01 Gy, yielding a dose modification factor of 1.34 +/- 0.01. Dihydrolipoic acid (reduced form) has no radioprotective effect in CD2F1 mice.