The Aberystwyth to Carmarthen and Cardiff bus service will end today after the company running it went into administration.
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Ceredigion-based Lewis Coaches has 30 vehicles, and the Confederation of Passenger Transport Cymru said 40 jobs were affected.
Welsh Government said Ceredigion council would probably maintain the services, including school transport.
Lewis Coaches is the third bus company in Wales to collapse in the last two months.
Wrexham-based GHA Coaches went into administration in July, a month after Pembrokeshire firm Silcox Coaches, ceased trading after 134 years.