The in situ distribution of NK cells in rat liver during the first 28 days of an experimental infection with F hepatica was investigated. NK cells were distributed homogeneously throughout the hepatic parenchyma in uninfected animals. The total number of hepatic mononuclear cells increased significantly following infection, but the proportion of NK cells did not change. After infection, these cells were found around the portal space, around the centrolobular vein, in the periportal fibrosis and in the band of collagen. However, no NK cells could be detected in or around the granuloma during infection. The frequency of both I L-2- and IFNgamma-producing NK cells was higher on day 7 postinfection (pi) but only the percentage of IFNgamma -CD161+ subsets remained elevated thereafter, whereas the percentage of both IL-2+CD161+ and IL-4+CD161+ subsets returned to the baseline. The number of CD161+IL10+ cells did not change significantly. These results suggest that NK cells could be another source for the early production of IFNgamma but provide no evidence that these cells are involved in early events associated with granuloma formation.