alpha-Endorphin (aEP) inhibited the expression of HLA-Class II antigens by PHA-primed T lymphocytes and reduced mitogen-induced T-cell proliferation up to 35%. This action was time related and not naloxone sensitive. When aEP was added to autologous and allogeneic lymphocyte cultures (both of non-T/T and T/T type), it inhibited lymphocyte blastogenesis up to 40%. These findings, indicating that aEP can influence some functions of immunocompetent cells, provide evidence for the functional interrelationship between the neuroendocrine and the immune systems.