The ability of cells isolated from bovine milk and peripheral blood to present soluble protein and particulate bacterial antigens to peripheral blood T lymphocytes was compared using a culture system which consistently supports antigen-specific, primary, proliferative responses. The present study shows that cells from blood and from milk can present antigen to unprimed T cells. Major histocompatibility complex class II restriction of the responses was demonstrated by abrogation of proliferation by the addition of anti-bovine class II monoclonal antibody to cultures. Although cells derived from blood or milk were shown to be capable of presenting antigen to T cells, differences in optimal culture conditions and kinetics of the resulting response were observed.