It is not known how the protein Bcl-2 inhibits cell death induced by calcium signalling and growth-factor withdrawal(1-3). Here we report that Bcl-2 forms a tight complex with calcineurin, resulting in the targeting of calcineurin to Bcl-2 sites on cytoplasmic membranes, and show that this interaction is dependent on the BH4 domain of Bcl-2. Calcineurin bound to Bcl-2 is an active phosphatase but is unable to promote the nuclear translocation of NF-AT, a transcription-factor required for induction of interleukin-2 expression, suggesting a mechanism by which Bcl-2 suppresses NF-AT activity(4). We also show that Bar, a pro-apoptotic member of the Bcl-2 family, interferes with interactions between calcineurin and Bcl-2. We propose that the ability of Bcl-2 to block NF-AT signalling is due to the sequestering of active calcineurin to the same domain of Bcl-2 which associates with Rad-1 (ref. 5), and that calcineurin may act in Bcl-2-regulated functions.