The ability of mouse amniotic fluid (MAF), alpha-foetoprotein (AFP) and MAF depleted of AFP (MAF - AFP) to suppress primary one-way MLR's was investigated. It was found that MAF, AFP and MAF - AFP were all suppressive of MLR's specific for MHC, K, D or I + S determinants. Suppression was observed when either lymph node or spleen cells were used as the responder cells. Nylon wool column passage of these cells did not significantly affect the immunosuppressive action of these substances. In contrast, MLR's specific for non-MHC/M-locus determinants demonstrated either diminished suppression or augmentation of the response, compared with the MHC stimulated MLR's. Our results show a differential effect of whole MAF and its fractions on the proliferative responses induced by various allogeneic stimuli and suggest that suppression is not due to a non-specific effect on proliferation regardless of the stimulus or cell type involved.