High-quality Tier 1 instruction is frequently conceptualized as the "foundation" for other tiers of intervention within multi-tiered systems of support (MTSS) models (Gersten et al., 2009). However, the vast majority of Tier 2 intervention studies do not account for Tier 1 variables when examining intervention effectiveness (Hill et al., 2012). The purpose of the current study was to examine Tier 1 predictors, or "quality indicators", of differential responsiveness to Tier 2 mathematics intervention. Data was drawn from a large-scale dataset where all teachers taught the Early Learning in Mathematics (Tier 1) core program across the academic year, and a subset of students were selected for the ROOTS (Tier 2) mathematics intervention. We examined the following Tier 1 variables: (1) classroom-level mathematics gains, (2) Tier 1 fidelity of implementation, (3) Tier 1 classroom management and instructional support, and (4) class size. Response to Tier 2 intervention was not significantly predicted by any of the Tier 1 variables examined, however the pattern of Hedges' g effect sizes suggested that students with higher quality of Tier 1 instruction tended to benefit less from the Tier 2 ROOTS intervention. Results are discussed in the context of implications for research and practice. [This paper will be published in the "Journal of Learning Disabilities."]