Police refused to give the news agency the volunteers' names, but Ghanaian media identified them as Andrew Kristler and Rachel Riccardi.
They are accused of killing one Najas Illiasu, known as "Ninja," in Wa in northern Ghana, according to the Ghana News Link website.
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Illiasu and an accomplice reportedly threatened the two Americans with a machete as they made their way home from a night club early on Saturday morning.
A struggle ensued, during which one of the Americans allegedly stabbed Illiasu with a pocket knife.
The attacker ran away, and his body was later found by passers-by, the Ghana MMA site said.
The US embassy in Accra confirmed to Reuters that two members of the Peace Corps were involved in "a safety and security situation," and that the police were investigating.
A police spokesman told the Associated Press that the two Americans had been released after questioning.
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