This study assesses the effects of adrenocorticotropic hormone (ACTH), alpha-endorphin (alpha-endo), beta-endorphin (beta-endo), and methionine-enkephalin (met-enk) on tetanus toxoid-stimulated in vitro specific antibody (anti-TT) synthesis. ACTH and TT-costimulated cultures enhanced antibody (Ab) synthesis over control TT-stimulated cultures at 10(-9) and 10(-11) M and suppressed Ab synthesis at 10(-13) and 10(-17) M. The alpha-endo and TT-costimulated cultures enhanced Ab synthesis over control cultures at all concentrations tested (10(-7) to 10(-15) M). Cultures costimulated with beta-endo and TT enhanced Ab synthesis over control cultures at 10(-11) M and suppressed Ab synthesis at doses above and below 10(-11) M. The met-enk and TT-costimulated cultures produced more Ab than controls at 10(-9) M; and the met-enk and TT-costimulated cultures produced less Ab than controls at other concentrations as low as 10(-17) M and as high as 10(-7) M. The results of this study provide one reason as to why the interactions between the neuroendocrine and immune systems remain unclear.