Cytotoxic T‐lymphocyte‐associated antigen (CTLA‐4) is an important downregulator of T‐cell activation. In order to analyze the expression and regulation of CTLA‐4 on human peripheral T cells, CTLA‐4 mRNA and protein expression were determined using analysis by reverse transcription–polymerase chain reaction (RT–PCR) and FACs, respectively. Intracellular CTLA‐4 was constitutively expressed in unstimulated CD4⁺ and CD8⁺ T cells. Interleukin (IL)‐2 induced a dose‐dependent increase of both intracellular and surface expression of CTLA‐4 (CD152). Most of the CD4⁺ and CD8⁺ cells expressing CTLA‐4 also expressed CD25. Interferon (IFN)‐γ induced the upregulation of CTLA‐4 expression via antigen‐presenting cells (APC) activation. The CTLA‐4delTM mRNA (550 bp) had a shorter half‐life than the full length CTLA‐4 mRNA and the expression was downregulated upon activation of the cells by treatment with IL‐2. Given an inhibitory role of CTLA‐4 and CD4⁺ CD25⁺ T cells in immune responses, the present findings suggest that IL‐2‐induced immunosuppression may result from its stimulatory effect of the CTLA‐4 expression.