Fish oil is believed to alter the immune response and improve survival after infections in experimental animals. This effect may be due to altered production of the leukotrienes (LT). We, therefore, performed a study in order to evaluate whether the effect of fish oil on the immune response of experimental animals is mediated through altered production of the LT. Female NMRI mice in four groups were fed with fish oil, fish oil with 5-lipoxygenase (5-LO) inhibitor (Zileuton, Abbott Laboratories, Chicago, IL, USA), corn oil or corn oil with 5-LO inhibitor. After 6 weeks, the mice were infected with Klebsiella pneumoniae and the survival was monitored. The experiment was performed twice. Analysis was performed mainly on data pooled from both experiments. The survival of the groups fed with fish oil was increased, compared to that of all the other groups and when compared to the groups fed with fish oil with 5-LO inhibitor (log-rank test) the difference was significant (P = 0.007). It has been postulated that the effect of fish oil on the immune system is mediated through altered production of LT. In our study, blocking of the production of the LT eliminated the beneficial effects of fish oil. Our results are in concord with the hypothesis that the effect of fish oil is, at least partly, mediated through altered production of LT.