In previous studies, we demonstrated that heavy metal stress has a marked effect on the susceptibility of grouper to a low pathogenic IPN virus infection. An immunotoxic effect caused by heavy metals may well account for the results. Studies were preformed in vitro and in vivo to examine the influences of zinc and cadmium on phagocytic activities of the head kidney phagocytes from grouper. Phagocytic activity was assessed by respiratory burst of the phagocytes and their capacity to phagocytose fluorescent latex beads. The production of superoxide anion (O2) in head kidney phagocytes was detected using the nitroblue tetrazolium (NBT) assay. Phagocytes were incubated in vitro for 2 h in medium containing 10^(-3) to 10^(-6) M of zinc chloride, and 10^(-4) to 10^(-7) M of cadmium chloride. Respiratory burst activity was decreased for all concentrations studied except 10^(-7) M of cadmium chloride. Phagocytosis results, however, had high variability. In vivo exposure for 4 days to zinc and cadmium separately by immersion inhibited O2 production of phagocytes from head kidney, as that observed in vitro. Attempts were also made to clarify the correlation between heavy metal and IPNV infection on phagocytic activities of head kidney phagocytes. Groupers were exposed to either five concentrations of heavy metals (zinc or cadmium) or virus infection, or both. The results obtained show that either heavy metal or virus infection caused a significant decrease in phagocytic activities of head kidney phagocytes. Phagocytic indexes appear lower in the groups of both heavy metal and IPNV treatment, but no significant differences were observed when compared with the results of heavy metal treatment alone.