In an attempt to elucidate the pathogenic role of a CD4⁺ cytotoxic T‐cell clone NT4.2 isolated from the bone marrow of a patient with cyclosporine‐dependent aplastic anaemia, we characterized the T‐cell clone as well as its cytotoxicity against an autologous Epstein‐Barr (EB) virus‐transformed B‐lymphoblastoid cell line (LCL). NT4.2 expressed BV21⁺ BJ2.7⁺ with a complementarity‐determining region (CDR) 3 motif of SQGQGEVEQY which was homologous to that of a T‐cell clone isolated from a patient with connective tissue disease. NT4.2 started to lyse LCL cells within 2 h and exerted maximal cytotoxicity within 3 h of incubation. The cytotoxicity required the presence of divalent cations and was not associated with DNA fragmentation of the target cells. Anti‐CD59 monoclonal antibodies (MoAb) blocked the cytotoxicity to the same degree as anti‐CD3, HLA‐DR or CD2 mAb. Flow cytometric analysis of the peripheral blood of this patient during remission after cyclosporine therapy revealed 1.7% of granulocytes to be deficient in CD59. These findings indicate that NT4.2 exerts its cytotoxicity through a perforin‐mediated pathway, not a Fas/Fas ligand‐dependent pathway, and that haemopoietic stem cells lacking CD59 may evade cytotoxic T lymphocytes, leading to the in vivo expansion of a paroxysmal nocturnal haemoglobinuria clone.