The effect of griseofulvin on porphyrin biosynthesis was studied in vitro and in vivo using liver and skin explants from mice. Neither porphyrin nor precursors accumulation was detected after in vitro treatment of explants with griseofulvin. Culture medium porphyrins formed from added delta-amino-laevulinic acid (ALA) were increased after oral chronic intoxication. Similar results were obtained by cutaneous and oral intoxication. Consequently griseofulvin topical application is proposed as an alternative method to produce experimental erythropoietic protoporphyria. Probable intoxication mechanisms are proposed to explain the porphyrinogenic action of griseofulvin.