The present reports the influence of bovine beta-casein on in vitro and in vivo immune responses. Bovine beta-casein showed an inhibitory effect on ovine neutrophil chemotaxis but had an enhancing effect on superoxide production by neutrophils. In response to mitogenic stimulation, the proliferative response of both T and B lymphocytes was significantly enhanced by beta-casein. While beta-casein had no significant effects on IFN gamma production by ovine blood lymphocytes, and TNF alpha production and MCH Class II antigen expression by ovine bronchoalveolar macrophages, it enhanced IL-1 beta production by the macrophages, beta-casein also had no influence on bovine NK cell activity against a virally-infected cell line. Interestingly, beta-casein was found to reduce the adjuvant effect of matrix immune stimulating complexes (ISCOM) on anti-ovalbumin antibody response in mice when given intramuscularly. Taken together, the results suggest that bovine beta-casein had selective modulating effects in vitro on both innate and adaptive immune responses in ruminants, whereas systemic administration of beta-casein, that might have a depressive effect on adjuvant activity, requires further study.