The objective of the study was to investigate the effects of estrogen on severity and duration of myoclonus in the rat cardiac arrest model of posthypoxic myoclonus. Female sex hormones affect a variety of movement disorders and alter dopaminergic and serotonergic pharmacology. Although women represented three-fourths of patients from the original report of Lance and Adams and 80% of the largest published series, the impact of estrogens on myoclonus has never been studied. Twelve previously ovariectomized female rats underwent 8 minutes of mechanically induced cardiac arrest and were resuscitated according to a standardized protocol. On the same day, they were randomly assigned to subcutaneous treatment with a 21-day, 0.5-mg, 17 &bgr;-estradiol or matching placebo pellet. Animals were tested daily with 7 sets of 45 auditory stimuli for 10 days, and myoclonus scores were obtained using a 5-point interval scale. Comparisons were based on two-sample Wilcoxon rank-sum tests. Estrogen treatment significantly enhanced myoclonus intensity and duration: mean peak myoclonus score, 210.2 ± 18.0 versus 180 ± 28.5 (p= 0.031); mean number of days above baseline, 9.2 ± 0.4 versus 5.7 ± 2.3 (p= 0.004); mean score on day 10, 90.7 ± 38.7 versus 27.0 ± 20.6 (p= 0.016). All estrogen-treated animals were above baseline on day 10 compared with none in the placebo group. Estrogen enhances and prolongs posthypoxic myoclonus, suggesting that female gender and estrogen status may play a pivotal role as a risk factor for human posthypoxic myoclonus.