To clarify the role of natural killer (NK) cells in acute hepatitis (AH) and fulminant hepatitis (FH), we measured the prevalence of CD16+ and CD57+ NK cells and the serum levels of IL-15, an inducer of NK cell activity. We analyzed 14 healthy subjects, 30 AH patients, and 13 FH patients for the percentages of CD16+ and CD57+ cells in peripheral blood lymphocytes and the serum IL-15 levels. In the AH patients with HAV, the percentage of CD16+ cells was significantly increased compared to healthy subjects, but that of CD57+ cells did not differ between the groups. The mean values of IL-15 levels of AH with HAV and unknown etiology, as well as of FH were higher than those of healthy subjects. Four subacute type FH (S-FH) patients had an increase in serum IL-15 levels, as well as the percentage of CD16+ cells throughout the course of their illness. However, in four acute type FH patients, this phenomenon was not observed. Our data suggest that NK cell immunity appears to be important in patients with AH secondary to HAV infection. In addition, the number of IL-15 and NK cells increased in the later stages of the illness, which may have contributed to the pathogenesis of S-FH.