Protective response was investigated in rainbow trout Oncorhynchus mykiss that had recovered from a primary low-dose cohabitation challenge of Loma salmonae and were re-challenged via a high dose oral exposure under experimental conditions. Compared to uninfected control fish, the previously exposed trout had 82.6% and 86.0% fewer xenomas, and many of the recovered fish (47% and 55%) showed no signs of infection whereas 95% and 100% of the control fish developed xenomas on their gills in two experimental tanks. From the results we conclude that rainbow trout develop protective immunity following low-dose exposure to L. salmonae acquired through cohabitation. The relevance of this with respect to unexpected patterns of disease presentation at commercial salmon farming sites is discussed.