The effect of hemin on the stability of delta-aminolevulinate (ALA) synthase mRNA was investigated in primary cultures of chicken embryo hepatocytes. Hepatocytes were first incubated with allylisopropylacetamide (AIA) to increase the starting level of ALA synthase mRNA, and then the cells were incubated with alpha-amanitin (1 microgram/ml) to block further transcription of ALA synthase RNA. The rates of depletion of the enzyme's mRNA were then determined by liquid hybridization analyses in cells incubated with or without hemin (10 microM) in the culture medium. The analyses indicated that hemin increased the rate of ALA synthase mRNA degradation. The half-life of the messenger in hepatocytes incubated with hemin was 80 min compared with 220 min in cells incubated without additional hemin in the culture medium. The results thus indicated a novel mechanism by which hemin modulated the biogenesis of ALA synthase in liver.