Sixty asymptomatic cigarette smokers were randomly allocated into three treatment groups. Smokers in Group 1 received 900 international units of Vitamin E (VE) daily for 6 wk, whereas 40 mg of beta-carotene (BC) daily was administered to those in Group 2 for the same period. Subjects in Group 3 were treated with a matched placebo. Plasma levels of VE and BC as well as circulating leukocyte counts, sister chromatid exchanges (SCEs), and the luminol-enhanced chemiluminescence (LECL) responses of blood phagocytes activated with phorbol myristate acetate (PMA) and FMLP with cytochalasin B (FMLP/CB) were measured prior to the administration of the antioxidant/placebo after 4 and 6 wk of supplementation and 12 wk after cessation of treatment. SCEs and leukocyte counts remained unchanged throughout the trial in all three treatment groups. Administration of VE for 4 wk was accompanied by decreased FMLP/CB-activated (p less than 0.005) and PMA-activated (p less than 0.005) LECL responses. However, with PMA as stimulant, the inhibition of LECL was transient, with partial recovery observed after 6 wk despite continued administration of VE. Administration of BC was associated with progressive inhibition of both FMLP/CB-activated (p less than 0.05 and p less than 0.01 after 4 and 6 wk, respectively) and PMA-activated (p less than 0.025 after 6 wk) LECL. No alterations in LECL responses were observed in Group 3 (placebo). VE appeared to inhibit the generation of oxidants by activated phagocytes, whereas BC scavenged oxidants generated by the myeloperoxidase/H2O2/halide system.