The effect of oral lentinan, a biological response modifier, on the control of systemic immune function was studied in six-week-old male Wistar-Imamichi specific-pathogen free rats. In the lentinan-treated group, 1 mg of lentinan dissolved in 1 ml of physiological saline was administered forcibly into the stomach twice weekly for four or eight weeks. Physiological saline alone was administered in a similar fashion to the control group. Leukocyte and lymphocyte counts were made and lymphocyte subsets measured using monoclonal antibodies W3/13, W3/25, and OX8, and a laser flow cytometry system. The T-cell level, the helper/inducer T-cell level, and the suppressor/cytotoxic T-cell level were measured. The peripheral leukocyte and lymphocyte counts did not change significantly in either group during treatment. After four weeks of treatment, however, the lentinan group had a significantly higher T-cell level, helper-cell level, and helper-suppressor ratio, and a significantly lower suppressor-cell level than did the control group. No significant between-group differences in the lymphocyte subsets or the helper-suppressor ratio were noted after eight weeks of treatment. Oral administration of lentinan appears to modulate the systemic immune function through stimulation of T cells, especially helper cells. Continued administration produced less effect, possibly due to a tolerance to the effect of lentinan.