The cytotoxicity of 8 natural dyes, commercially available as food additives in Japan, was studied on cultured fetal rat hepatocytes. Laccaic acid, one of the carminic acid samples and monascus pigments were found to be very toxic to cultured hepatocytes. Laccaic acid caused an increase in gamma-glutamyl transpeptidase activity. An 11-fold increase was seen 4 days after such addition, a significantly greater elevation than that produced by either the water or acetone solvents employed, or other dyes which have no toxic effects. On the other hand, monascus pigments had an increasing effect on both gamma-glutamyl transpeptidase and glutathione S-transferase, the later enzyme being elevated approximately 9 times greater than control values within 2-4 days. The increases in gamma-glutamyl transpeptidase and glutathione S-transferase activities by laccaic acid and monascus pigments could be inhibited by the simultaneous addition of either actinomycin D or cycloheximide. This suggests that the induction of these enzymes requires transcription and translation processes.