Antigen-primed T-cell blasts may be separated from alloreactive T cells on Percoll gradients. By means of this method, HLA restriction of antigen-specific proliferative T-cell responses may be studied, using allogeneic antigen-presenting cells carrying foreign D/DR antigens. The reported data confirm that the D/DR molecules as such are major restriction elements in the T-cell response to herpes simplex virus (HSV) and purified protein derivative (PPD). However, evidence is presented that other Class II HLA molecules, the MT molecules, may also function as restriction elements for the HSV response.