Transferrin and albumin, which are both secreted from the human hepatoma cell line Hep3B, were regulated transcriptionally by retinoic acid (RA) in a dose-dependent manner. The cell growth rate was little affected under the same conditions. The treatment of Hep3B cells with RA (10 microM for 48 h) resulted in an 8-fold increase in transferrin protein synthesis, a 10-fold increase in the steady-state transferrin mRNA level, and a 5-fold increase in its transcriptional rate. The same treatment led to 4-fold decrease in albumin synthesis, as well as a 7-fold decline in the steady-state albumin mRNA level and a 4-fold decrease in the transcriptional rate. Cycloheximide and actinomycin D blocked the action of RA, suggesting that RA may regulate transferrin and albumin gene expression indirectly in human liver cells.