Primary cultures of fetal rat hepatocytes were maintained in an arginine-free medium deprived of serum but supplemented with 0.03 mM L-ornithine and 10(-8) M dexamethasone. Ferric nitrilotriacetate was added to the culture medium in order to obtain iron concentrations ranging from 10 to 100 microM. After 24 h of treatment, iron was visualized inside the hepatocytes by the staining method of Perls and electron microscope study. The present data demonstrate that iron overload decreases transferrin secretion; this effect appears not to be specific, since albumin production is affected in a similar manner. This depressed transferrin secretion is not the consequence of hepatocyte death, as the phenomenon is confirmed when expressed per cell. Since the corresponding mRNA is unaffected, it may be postulated that iron overload decreases transferrin secretion at some post-transcriptional level.