The human high-affinity receptor for interleukin 2 (IL-2) has been proposed as being a membrane complex composed of at least two distinct polypeptide chains: p55 (alpha chain), recognized by the anti-Tac monoclonal antibody (mAb), and p75 (beta chain), both of which are capable of binding IL-2. Whereas the alpha chain itself has been shown to be nonfunctional, the beta chain appears to be pivotal in the IL-2 signal transduction, although the beta chain is otherwise poorly characterized. Three beta chain-specific mAbs, designated Mik-beta 1, -beta 2, and -beta 3, were developed. Mik-beta 1 and -beta 2 completely inhibited the IL-2 binding to the beta chain, whereas Mik-beta 3 immunoprecipitated the beta chain crosslinked with 125I-labeled IL-2. The beta chain immunoprecipitated by these mAbs was revealed to have a Mr of 68,000-72,000. High-affinity IL-2 binding was completely abolished by Mik-beta 1. Although IL-2-dependent T-cell growth at high IL-2 concentrations was not inhibited by the anti-Tac, it was almost completely inhibited by Mik-beta 1 in the presence of the anti-Tac. These results clearly indicate that the beta chain is an indispensable component to the high-affinity IL-2 receptor and is responsible for the IL-2 signal transduction. The beta chain was found to be constitutively expressed without the alpha chain on the surface of peripheral blood Leu-19+ natural killer cells.