This investigation compared quantitative outcomes associated with class-wide peer tutoring using differentiated hands-on activities vs. teacher-directed instruction for students with mild disabilities in inclusive 8th-grade science classes. Thirteen classes of 213 students (109 males; 104 females), of whom 44 were classified with disabilities, participated in 12-week sessions in a randomized field trial design. Experimental classes received units of differentiated, peer-mediated, hands-on instruction, while control classes received traditional science instruction. Results indicate that collaborative hands-on activities statistically facilitate learning of middle school science content on posttests and on state high-stakes tests for all students and that students enjoyed using the activities. Implications for practice indicate use of supplemental peer mediated hands-on activities may provide necessary review and practice for students with disabilities. Future research would help uncover additional critical instructional variables.