Bacterial kidney disease has consistently resisted attempts to control it by prophylactic immunisation. Although successful vaccines have been produced to a number of Gram-negative fish pathogens, the relatively simple method used in these cases have not been successful with Renibacterium salmoninarum. A more circumspect and thorough knowledge of the biological function of R. salmoninarum antigens must be obtained. Also required is a more precise understanding of the role of regional immunity in effective prophylaxis. Aspects of R. salmoninarum's biology provide a provocative challenge to the vaccinologist. Its residence in, and apparent commandeering of the macrophage, indicate that a vigorous cell-mediated response will probably be required to generate protective immunity. Its most biologically potent secreted product, p57, appears to be an aggressin. Further, p57 has the capability of frustrating immunoprophylaxis by either misdirecting the immune response, or by preventing its induction. Many immunization studies have used injection immunization and challenge protocols. It now appears that alternative routes of immunization which had been considered less protective (i.e. oral immunization) may not only be more efficacious, but may be the only route that does not lead to a misdirected and possibly pathological immune response. Also, the general reliance on serum antibodies as the only means to assess immunity is fraught with difficulties, particularly with pathogens such as R. salmoninarum. Recent advances in the analysis of cellular immunity will be a great aid in the design of future vaccines.