We have studied three patients with ataxia-telangiectasia (AT) and found two of them to have a normal mixed leucocyte culture stimulating and responding ability. However, all three patients and one parent had defective cell-mediated lympholysis (CML), even in the face of a potent proliferative response to allogeneic leucocytes. None of these patients showed significant proliferative responses to common microbial antigens (tetanus toxoid, Candida albicans, purified protein derivative (PPD), diphtheria toxoid, influenza). Our studies indicate tha the T cell defect in AT preferentially affects certain T cell functions associated with antigen recognition and the generation of allogeneic CML, while sparing the allogeneic proliferative response. The selective deficiency of specific lymphocyte functions in a thymic immunodeficiency with a known defect in DNA repair is consistent with the concept that DNA modulating enzymes are important for T cell function.