Men have floated out the hatch on all 420 spacewalks conducted over the past half-century.
That changes Friday with spacewalk No. 421.
NASA astronauts Christina Koch and Jessica Meir will make "HERstory," as NASA is calling it, with the first all-female spacewalk. All four men aboard the International Space Station will remain inside, as Koch and Meir go out to replace a broken battery charger.
Koch and Meir will make their way outside the hatch around 7:50 a.m. ET, NASA says.
The space agency is streaming the event live, starting at 6:30 a.m.
The battery charger failed after Koch and a male crewmate installed new batteries outside the space station last week. NASA put the remaining battery replacements on hold to fix the problem and moved up the women's planned spacewalk by three days.
NASA says the charger is one of many that help provide power to the space station and its failure has not impacted the station's operations or crew.
The spacewalk by Meir and Koch could last up to six hours. The four men aboard the International Space Station will remain inside during it.
Since the first spacewalk in 1965, there have been 227 spacewalkers, only 14 of them women.
Russia holds claim to the first spacewalk in 1965 and also the first spacewalk by a woman in 1984. The U.S. trailed by a few months in each instance.
NASA says Friday's all-women spacewalk marks a milestone for the agency, as it aims to send a woman to the moon by 2024.
It's also a milestone for Meir; Friday's spacewalk will be her first.
The marine biologist who arrived at the orbiting lab last month, will be the 15th female spacewalker. Koch, an electrical engineer, has already completed three spacewalks; she's seven months into an 11-month space flight that will be the longest by a woman.
NASA planned the first all-female spacewalk in March, but called it off because there weren't enough medium-sized spacesuits to fit the women. Koch put together a second medium-sized spacesuit over the summer.
Meanwhile, NASA is asking school teachers to share photos of their students celebrating "HERstory in the making." The pictures might end up on the spacewalk broadcast.
With files from CBC News
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