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Welsh firm Morgan Bruce and Oxford's Cole & Cole will merge in November, creating a top 25 firm by size with an annual revenue of £30m.
The new 92-partner firm will be called Morgan Cole and will unite Morgan Bruce's offices in Swansea, Cardiff, Newport and London with those of Cole & Cole in Oxford, Reading and Croydon.
The firm will be the largest practice in the competitive market of the Thames Valley/M4 corridor.
With its high concentration of major multinational and high-tech companies, the region has long been a battleground between City, West Country and local firms. Bristol and London firm Osborne Clarke opened in Reading last year.
The combined revenues of the firms last year would have placed Morgan Cole 42nd in The Lawyer's top 50, compiled in August.
Morgan Bruce - the largest firm in Wales, with 57 partners each drawing average profits of £135,000 - has been openly looking for a merger partner for some time.
The tie-up with Cole & Cole will be its third merger in the past four years. In autumn 1994 it took over 11-partner London firm Binks Stern and last year it merged with Newport practice Guthrie Francis.
The smaller 35-partner Cole & Cole, whose per partner profits stand at around £110,000, is particularly well-known for litigation, commercial property and employment, and has an improving corporate practice. It also has a Croydon insurance practice and an office in Reading.
Morgan Bruce chief executive David Main, who will also be chief executive of the merged firm, did not rule out further mergers.
"It would be premature to announce future plans at this stage, but we are keen to see the size of the London operation grow," he said.
Morgan Bruce chairman John Bowen and Cole & Cole senior partner John Moisson will be joint chairmen of the firm, whose 12-member management board will have equal representation from the two firms.
An election to choose a single chairman will be held after an interim period.
Moisson said: "The merger gives us the advantage of greater investment in monetary terms and also in people. We are very enthusiastic about it - we do not regard it as a takeover."
Michael Sippitt, managing partner at leading Reading firm Clarks, commented: "It is good for all of us who are trying to demonstrate the quality of services outside London."