The occurrence of brown ring disease (BRD) in farmed Manila clams Ruditapes philippinarum is seasonal. Development of the disease is believed to require the presence of the infective agent Vibrio tapetis and particular environmental conditions. This paper studies the effect of salinity (20 to 40‰) on measurable immune parameters of Manila clams, and the progression of BRD in experimentally infected individuals. At 20‰ salinity, the total haemocyte count was reduced and disease prevalence was highest. At 40‰ salinity significantly fewer clams presented signs of BRD, and this was correlated with increases in the total haemocyte count, hyalinocyte count, phenoloxidase levels and phagocytic activity of haemocytes. Inoculation of clams with V. tapetis did not have a significant effect on the immune parameters measured. Thus, this laboratory-based study relates environmental stress to disease development.