The relative amount of apolipoprotein (apo-) E mRNA in 12 different tissues of the rat and marmoset was examined by dot blot hybridization using cloned cDNA probes. As expected, it was found to be most abundant in the liver. However, substantial amounts of apo-E mRNA were found in the brain and adrenals at relative levels about one-third of that found in the liver. Significant quantities of apo-E mRNA were detected in all of the other peripheral tissues as well. The apo-E mRNA levels in these tissues were 2-10% of that found in the liver of the rat and 10-30% of that found in the liver of the marmoset. Apo-E mRNA was also abundant in human brain and in each species examined; it was distributed throughout all major areas of this organ. In contrast, apo-A-I mRNA was detected in abundant amounts only in the small intestine and in the liver. Extrahepatic apo-E mRNA appears to be functional, generating a translation product similar or identical to that generated by the liver. During fetal and neonatal development, apo-E mRNA is rapidly induced from low levels to approximately equal to 60% of adult levels in liver at parturition. The fetal yolk sac contains more apo-E mRNA than the fetal liver, suggesting a significant role for the yolk sac as a source of apo-E during gestation.