Cat’s claw (Uncaria tomentosa) is a medicinal plant from the Amazon River basin that is widely used for inflammatory disorders and was previously described as an inhibitor of NF-kB. Cat’s claw was prepared as a decoction (water extraction) of micropulverized bark with and without concentration by freeze-drying. Murine macrophages (RAW 264.7 cells) were used in cytotoxicity assays (trypan blue exclusion) in response to the free radical 1,1-diphenyl2-picrilhydrazyl (DPPH, 0.3 mM) and ultraviolet light (UV) light. TNFa production was induced by lipopolysaccharide (LPS 0.5 mg/ml). Cat’s claw was an effective scavenger of DPPH; the EC50 value for freeze-dried concentrates was significantly less than micropulverized (18 vs. 150 mg/ml, p , .05). Cat’s claw (10 mg/ml freeze-dried) was fully protective against DPPH and UV irradiation-induced cytotoxicity. LPS increased TNFa media levels from 3 to 97 ng/ml. Cat’s claw suppressed TNFa production by approximately 65–85% (p , .01) but at concentrations considerably lower than its antioxidant activity: freeze-dried EC50 5 1.2 ng/ml, micropulverized EC50 5 28 ng/ml. In conclusion, cat’s claw is an effective antioxidant, but perhaps more importantly a remarkably potent inhibitor of TNFa production. The primary mechanism for cat’s claw anti-inflammatory actions appears to be immunomodulation via suppression of TNFa synthesis.