Reed Smith, which was founded in Pittsburgh in the United States but has its biggest office in London, has confirmed it is in talks to merge with Philadelphia-based Pepper Hamilton.
"Based on these preliminary discussions, we see many potential benefits to joining forces," said Reed Smith in a statement.
"There remains a significant amount of work to do with Pepper Hamilton to assess those benefits and before any transaction would be ready to bring to the Reed Smith partnership."
Pepper Hamilton also confirmed the discussions.
A spokesman said: "These talks are in the early stages and will require a substantial amount of additional consideration on our part before we are prepared to bring this transaction before the Pepper partners for full consideration."
Elsewhere, City law firm Clyde and Co has confirmed its interest in expanding further into the US.
A spokesman for the firm said: "Our ambition is to have a presence in all the key insurance centres in the US and the Americas and we continuously study the market for opportunities.
"We only comment as and when discussions are positively concluded."
Mergermarket figures show there were four law firm M&A deals announced in the first quarter of this year, with a total value of $268m.