To evaluate the adverse effects of exogenously induced reactive oxygen species (ROS) on mouse embryo development by using the 12-phorbol 13-myristate acetate (PMA)-activated leukocyte model as a source of ROS, and to examine the protective effect of antioxidant supplementation (vitamin C and vitamin E). Prospective study. Research laboratory. Effects of ROS on the blastocyst development rate in the presence and absence of antioxidant supplementation. After incubation with the PMA-activated leukocyte supernatant, the median (25th, 75th percentile) rate of blastocyst development significantly decreased from 73% (60%, 80%) after 3 hours to 30% (20%, 40%) after 6 hours compared with control reactions (86% [80%, 100%]). Co-incubating the embryos with vitamin C (50 microM) and the PMA-activated supernatant significantly increased the blastocyst development rate from 73% (60%, 80%) to 90% (80%, 91%) at 3 hours and from 30% (20%, 40%) to 91% (89%, 91%) at 6 hours-a level similar to that of control reactions. The blastocyst development rate increased after vitamin E supplementation (400 microM) at 6 hours, but not significantly and not by as much as after vitamin C supplementation. Exposure of mouse embryos to ROS for extended periods results in embryotoxicity. Vitamin C is more effective than vitamin E in reversing ROS-induced mouse embryo toxicity.