The case involves 17-year-old Gavin Grimm, who was born a female but identifies as a male. Grimm filed suit to be allowed to use the boys' bathroom at his high school in Gloucester County, Virginia.
Arguments in the politically charged question will be heard between now and late June, making it easily one of the highest-profile cases set for the court's current term.
The Obama administration has said public schools should grant access to toilets and locker rooms based on the gender with which a student identifies, not the birth gender.
But more than a dozen Republican-controlled states, bitterly opposed to that approach, are challenging the federal government in court.
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Some conservatives see the directive from Washington as improper interference in local school affairs and an abuse of executive power.
Leading the opposition, North Carolina adopted a law requiring that transgender people use toilets corresponding to the gender on their birth certificates.
That law, affecting a tiny minority of the population -- less than 1 percent, according to some studies -- has been condemned as discriminatory by leading figures from civil society, from the business and sports worlds, and from the Democratic Party.
With four conservative and four liberal justices, the chances of tie votes -- and thus of weakly-worded decisions -- become greater, especially on such ideologically charged topics as this.