Dietary effects of a nucleotide mixture that contained AMP¡BGMP¡BCMP¡BUMP and IMP in equivalent amount were evaluated in 4 supplemental levels of 0, 0.05, 0.2, and 0.4 g/100g diet. Weight gain (519-616%) of juvenile groupers fed for 14 weeks with the test diets was not significantly affected by the supplements. Serum concentrations of total protein, albumin, and cholesterol, A/G ratio and activities of AST were also not significantly affected. Serum total bilirubin concentration in the 0.4 g/100g group was significantly higher than the 0 or 0.05 g/100g group. Head-kidney macrophage phagocytosis and intracellular superoxide anion production as well as serum lysozyme activity were also not different among treatments. Histological sections of fish gut indicated that villous heights of intestinal fold were significantly greater in the 0.2g/100g group than the 0.4 g/100g group, muscle layer thickness, in contrast, was not affected. When challenged with Photobacterium damsela subsp. damselae after fed the test for 3 weeks, relative percent survivals of the groupers were 87.8, 91.1, 90.0 and 94.4% (0, 0.05, 0.2, and 0.4 g/100g diet, respectively). The survivals were 74.5, 82.4, 86.3, and 85.3%, respectively when the feeding trial was extended to 18 weeks. The results show that a diet containg 38% protein and asupplemented with nucleotides at the tested levels was not effective in promoting growth, but was moderately effective in enhancing immune responses and pathogen resistance of juvenile grouper.