Atlantic salmon smolts challenged intraperitoneally (ip) and by cohabitation with a highly virulent strain of infectious pancreatic necrosis virus showed strong activation of important immune genes in spleen, liver, head-kidney and gill measured by real-time quantitative PCR. The genes investigated were IL-1beta, IL-10, IFN-alpha, IFN-gamma, Mx, MHC-I, MHC-II, TCR-alpha, CD8-alpha and mIgM. A low final cumulative mortality of about 10% was seen in the ip-challenged group, while more than 40% of the cohabitants died in the sampling period. Sampling was performed at day 15, 24 and 37 post ip-challenge. Overall, the expression of the investigated genes varied highly. The expression of IL-1beta, IL-10, MHC-II, TCR-alpha, CD8-alpha and mIgM showed more or less the same patterns between the two groups of fish by being significantly upregulated at day 24 post ip-challenge. However, the degree of regulation varied a lot among the genes. A pattern showing differences between ip-challenged and cohabitants were seen for IFN-gamma and especially IFN-alpha, where the upregulation seemed to last longer for the cohabitants. The Mx gene was the most induced gene, but also the one with highest individual variance. Mx but also MHC-I were both still highly upregulated at the last sampling point within both groups of fish. The results seem to indicate that the differences in expression pattern(s) could reflect the different routes of entrance of the virus into the fish. This could maybe explain the different kinetics in the onset and the degree of mortality or the potential different molecular mechanisms used for combating the virus.