Addition of hydrocortisone to the rat mammary gland myoepithelial cell line, G4.2.3, induces the synthesis and secretion of alpha 2-macroglobulin. Interleukin-1 beta, interleukin-6 and transforming growth factor-beta synergize with hydrocortisone, increasing the synthesis of alpha 2-macroglobulin 2- to 4-fold, although they have no effect in the absence of hydrocortisone. Interleukin-6 is the most potent inducer having an optimum concentration of 1 ng/ml. Interleukin-6, unlike interleukin-1 beta or transforming growth factor-beta, decreases the lag phase from 10 h to 4 h before alpha 2-macroglobulin synthesis is induced by hydrocortisone. These results suggest that the mechanism of activation of transcription of the alpha 2-macroglobulin gene in mammary myoepithelial cells might differ from that operating in hepatic cells.