The sites of alpha 2‐macroglobulin mRNA synthesis during rat development have been localized by in situ hybridization using a rat alpha 2‐macroglobulin cDNA probe. Fetal liver was found to be the major site of alpha 2‐macroglobulin mRNA synthesis. In addition, alpha 2‐macroglobulin mRNA was detected in brain, spinal cord and eye. Alpha 2‐Macroglobulin mRNA was quantitated by use of a sensitive RNAse protection assay. Maximal levels of alpha 2‐macroglobulin mRNA were found in fetal livers shortly before birth. A rapid decline of alpha 2‐macroglobulin mRNA occurred within 1 day after parturition. A similar time course, although at an approximately 20‐fold lower level, was observed for alpha 2‐macroglobulin mRNA in livers of pregnant rats. Alpha 2‐Macroglobulin mRNA could also be detected in placenta. The levels were comparable to those found in maternal livers.