In 2001, N fertilizer prices nearly doubled as a result of increased natural gas prices. This was further troubling when considering that the world N use efficiency (NUE) in cereal grain production averages only 33%. Methods to improve NUE in winter wheat (Triticum aestivum L.) have not included high spatial-resolution management based on sensed plant growth properties nor on midseason prediction of grain yield. Our objective was to determine the validity of using in-season estimates of grain yield (INSEY) and a response index (RI) to modulate N at 1-m(2) spatial resolution. Four winter wheat field experiments were conducted that evaluated prescribed midseason N applications compared with uniform rates that simulated farmer practices. Our methods recognize that each 1-m(2) area in wheat fields needs to be sensed and managed independently and that the need for fertilizer N is temporally dependent. Averaged over locations, NUE was improved by >15% when N fertilization was based on optically sensed INSEY, determined for each 1-m(2) area, and a RI compared with traditional practices at uniform N rates.