Phycocyanin is a biliprotein which exerts antioxidative and anti-inflammatory effects in various in vivo and in vitro experimental models. In this study phycocyanin effects on tumor necrosis factor-alpha (TNF alpha) and nitrite levels in serum of mice treated with lipopolysaccharide (LPS) was examined. TNF alpha was measured by cytotoxicity on L-929 cells and nitrite by the Griess reaction, after reduction of all nitrates to nitrites by nitrate reductase, 1 h after LPS injection (0.5 mg/kg i.p.) there was a significant increase in TNF alpha levels in mouse serum. Phycocyanin (50-300 mg/kg p.o.), administered 1 h before LPS, reduced dose-dependently the TNF alpha concentration in serum. After 18 h, LPS (30 mg/kg i.p.) also induced a substantial increase in serum nitrite levels, which were reduced dose-dependently by phycocyanin pretreatment (100-300 mg/kg p.o.). The results indicate that phycocyanin exerts inhibitory effects on TNF alpha and NO production which might be ascribed to the antioxidative properties of the biliprotein.