In this study, adaptive immune response was investigated in farmed southern bluefin tuna, Thunnus maccoyii, infected with a sanguinicolid Cardicola forsteri. A cohort (Cohort(2005)) of southern bluefin tuna was sampled between March 2005 and August 2006. Samples were taken at the transfer of wild caught tuna to sea cages and then at regular intervals. Parasite intensity, abundance and prevalence data were recorded. An ELISA was developed to detect and quantify an antibody response against the blood fluke in southern bluefin tuna serum. Intensity and prevalence of the blood fluke were shown to peak in May 2005 at 10.9 flukes per infected fish (SE=1.72) and 97.5% prevalence and then decreased to low prevalence (10%) and intensity (1.0). There were no significant changes in prevalence or intensity in 2006. Antibody titres and seroprevalence increased from 1.37 U microl(-1) and 10% at transfer in March 2005 to reach a peak in December 2005 of 25.86 U microl(-1) (SE=6.26 U microl(-1)) and 66.66%. No significant changes were observed in antibody titres for the same cohort of fish during 2006. Parasitological and serological values from Cohort(2005) were compared to a 2006 cohort (Cohort(2006)) in March 2006 and August 2006 to determine if prior infection in Cohort(2005) elicited any protection against infection in 2006. Although significant differences were not observed in intensities between cohorts it was shown that Cohort(2005) had significantly lower abundances and prevalences of blood fluke infection than Cohort(2006). Although there was no significant difference in mean antibody titres between cohorts in March 2006, the mean antibody titre of Cohort(2006) was significantly greater than that of Cohort(2005) in August 2006. No significant differences were observed in seroprevalence. This is one of the few studies to demonstrate the development of acquired resistance in fish against a parasite in an aquaculture environment under natural infection conditions.