Three leading US senators have warned Egypt that the risk of a "disastrous" break in ties has rarely been greater.
John McCain, Kelly Ayotte and Joe Lieberman said the government in Cairo was exacerbating tensions in order to "advance a narrow political agenda".
On Sunday, Egypt said it would put on trial 43 pro-democracy activists, 19 of them Americans, over the funding of non-governmental organisations.
The ruling military council has accused them of stirring up unrest in Egypt.
The US state department said it was deeply concerned by the development and was seeking clarification from the Egyptian authorities.
Washington currently provides $1.3bn in military aid and about $250m in economic aid every year to Egypt, its most important Arab ally.
'Done nothing wrong'
In a statement, the senators warned that US Congressional "support for Egypt - including continued financial assistance - is in jeopardy".
"A rupture in relations would be disastrous, and the risks of such an outcome have rarely been greater," they added.
"The current crisis with the Egyptian government has escalated to such a level that it now threatens our long-standing partnership."
"There are committed opponents of the United States and the US-Egypt relationship within the government in Cairo who are exacerbating tensions and inflaming public opinion in order to advance a narrow political agenda."
They called for an end to the "harassment and prosecution of the employees of US non-governmental organisations operating in Egypt".
The senators' comments came after an Egyptian delegation abruptly cancelled meetings with them and other politicians in Washington.
The White House has also warned that putting the American activists on trial will have consequences for bilateral relations.
It said the individuals involved had "done nothing wrong", adding: "Their only assignment is to support Egypt in its transition to democracy."
The 19 Americans - including the son of US Transportation Secretary Ray LaHood - and 24 other pro-democracy activists were referred to trial before a criminal court in Cairo on Sunday on accusations that they set up branches of international organisations without a licence from the Egyptian authorities and received illegal foreign funding.
The International Republican Institute (IRI) and the National Democratic Institute (NDI) - loosely associated with the US Republican and Democratic parties - were among 17 US-based and local foreign-funded groups whose offices were raided by Egyptian prosecutors in December.
Correspondents say the raids were seen as an attack on free speech and an attempt by the Supreme Council of the Armed Forces (Scaf) to silence critics of its attempt to put down ongoing protests.