DNase I inhibition assay was used to determine the change in monomeric actin (G-actin) in human peripheral blood leukocytes following their treatment with phorbol esters and retinoids. Treatment of polymorphonuclear leukocytes (PMN) with 10(-6) M phorbol myristate acetate resulted in a decrease in G-actin content to 3.8 +/- 0.49 (microgram G-actin/100 micrograms total protein; mean +/- S.E.M.) from a control value of 5.6 +/- 0.51 (P less than 0.05). The effect of retinoic acid on mononuclear leukocytes varied depending on the concentration of the drug used. At 10(-5) M there is a slight increase in the amount of G-actin and maximal decrease in G-actin was noted at 10(-6) M. The decrease in G-actin can be prevented by pretreatment of cells with cytochalasin E (CE) indicating that the decrease is due to actin polymerization. The total actin, determined after guanidine hydrochloride (G X HCl) treatment, remained unchanged in drug treated cells. Only phorbol esters which are capable of inducing tumor promotion induce actin polymerization, suggesting that actin polymerization might have a role in tumor promotion. Actin polymerization might serve as a useful framework for further studies on delineating the mechanism of action of phorbol esters and retinoids.