Immunobiological effects of nivalenol (NIV), a trichothecene mycotoxin produced by Fusarium nivale, were examined in male F344 rats after 90-day dietary exposure at doses of 0, 0.4, 1.5, and 6.9 mg/kg body weight/day (0, 6.25, 25 and 100 ppm, respectively) in a subchronic toxicity study. With regards to the serum immunoglobulin levels, a slight increase of IgM was observed only at 6.9 mg/kg (26% increase), while levels of IgG and IgA did not fluctuate at any dose. Flow cytometric analysis of splenic cells revealed a dose-dependent decrease of T lymphocyte/B lymphocyte (CD3(+)/B220(+)) ratio from 1.5 mg/kg and an elevated CD4(+)helper/CD8(+)cytotoxic T lymphocyte ;ratio at 6.9 mg/kg. Furthermore, increases of natural killer (NK) activity of splenic lymphocytes against YAC-1 target cells were observed at all doses, while the magnitude of changes was similar between 1.5 and 6.9 mg/kg. At 6.9 mg/kg, the reduction of the ratio of NKR-P1A(+) splenic cells, which is an indicator of NK cells in the spleen, was apparent. As with other previous studies of NIV, decreased body weight was observed from 1.5 mg/kg during the experiment in the present study. In summary, NIV affected immune function in rats after 90-day dietary exposure, the effects being apparent from 0.4 mg/kg judging from the increase of NK activity, although nutritional suppression might have influenced the immunological changes appeared from 1.5 mg/kg. (C) 2007 Elsevier Ltd. All rights reserved.