We investigated the effect of aldosterone on Src kinase. In the kidney cell line, M-1 aldosterone leads to a >2fold transient activation of Src kinase seen as early as 2 min after aldosterone administration. Maximal Src kinase activation was measured at an aldosterone concentration of 1nM. In parallel to activation, autophosphorylation at Tyr-416 of Src kinase increased. Src kinase activation was blocked by spironolactone. Aldosterone led to increased association of Src with HSP84. Furthermore, rapamycin blocked aldosterone-induced Src activation. We conclude that Src activation by aldosterone is mediated through the mineralocorticoid receptor and HSP84. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.