Clifford Forsythe, the Ulster Unionist Party Member of Parliament for South Antrim, died on 27 April 2000, precipitating a by-election.
The election arose after the Good Friday Agreement, with prisoner releases having started, but before the pro-agreement parties had reached agreement on the shape of a devolved government. After a disputatious selection contest, the London-based public relations executive David Burnside was selected as the new Ulster Unionist Party candidate. Burnside claimed to have supported the Agreement at the time of its negotiation but to have since turned against the way in which it was being implemented. However this was at odds with his party's policy. This was seized upon by the Democratic Unionist Party candidate, former Mid-Ulster MP Rev. William McCrea in campaigning. McCrea campaigned on a policy of refusal to co-operate with Sinn Féin in the absence of progress on arms decommissioning.
The Northern Ireland Unionist Party initially selected Norman Boyd, who was a local member of the Northern Ireland Assembly (elected as a member of the United Kingdom Unionist Party). However, during the campaign Boyd withdrew, urging voters not to divide the anti-agreement vote, and supported McCrea. Although the Progressive Unionist Party had secured 8.7% of the vote at the previous general election, they did not stand on this occasion.