Oxford United trailed Kidderminster Harriers in the first half of their FA Carlsberg Trophy quarter-final at the Kassam Stadium.
Brian Smikle put Harriers in front from close range in the 17th minute, from Damian Spencer's low right-wing cross, after the visitors had broken swiftly from an Oxford corner.
Chris Wilder made six changes to the United side that had beaten Rushden in the Blue Square Premier on Tuesday with Chris Hargreaves, Rhys Day, Ryan Clarke and Sam Deering among those rested.
But the U's still had a strong line-up.
Mark Creighton headed against the top of the bar and keeper Ross Atkins saved from Simon Clist's volley in the opening 45 minutes.
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