In order to study a possible immunomodulatory effect of the royal jelly (RJ) secreted by mandibular and hypopharingeal glands of the worker honeybee (Apis mellifera Linné.) we have used a well established rodent model. The CBA mice were given s.c. 0.1 ml of RJ, 7 days before, or immediately after, the immunization with sheep red blood cells (SRBC). The Y59 rats received i.m. 0.4 ml or i.v. 0.025 ml of RJ once or twice at 7 day intervals. Serum levels of total proteins and immunoglobulins in the rats that received RJ once or twice within a 2-week-period were significantly lower (P < or = 0.05) as compared with the nontreated animals. In mice which were immunized with 4 x 10(8) of SRBC 7 days after the application of RJ the number of plaque forming splenocytes was significantly higher (P < or = 0.05) than that in the controls. Both the weight of inguinal lymph node and the number of peripheral blood lymphocytes were increased (P < or = 0.05) in RJ-treated mice 3 or 5 days after the immunization, respectively. Neutrophils were decreased (P < or = 0.05) in the mice that were killed 5 or 10 days after the RJ treatment. Overall these results indicate that RJ exhibited immunomodulatory properties by stimulating antibody production and immunocompetent cell proliferation in mice or depressing humoral immune functions in rats. Both phenomena, though species-related in this model, could probably be reversed by changing the dose or the route of RJ application.