Using a mixed-methodology, longitudinal design, individual differences and contextual factors related to differential response to general education instruction were examined. We tested a response-to-instruction model reflecting the first three phases of a model proposed by Fuchs and Fuchs (1998). We classified first- and second-grade children at-risk for reading problems into one of three responsiveness groups and compared groups on reading, phonological processing, behavioral, and instructional context measures. Further, we examined qualitatively the interaction of individual differences and instructional context. The most persistently nonresponsive group scored significantly lower on all individual difference measures, but did not experience poorer instructional settings. Further, this group demonstrated greater difficulty learning in the general education setting. The response-to-instruction model demonstrated construct and social validity with implications for an improved prereferral system. (Contains 5 tables and 2 footnotes.)