This study examined the impact of cooperative learning activities on student achievement and attitudes in large-enrollment (greater than 250) introductory biology classes. We found that students taught using a cooperative learning approach showed greater improvement in their knowledge of course material compared with students taught using a traditional lecture format. In addition, students viewed cooperative learning activities highly favorably. These findings suggest that encouraging students to work in small groups and improving feedback between the instructor and the students can help to improve student outcomes even in very large classes. These results should be viewed cautiously, however, until this experiment can be replicated with additional faculty. Strategies for potentially improving the impact of cooperative learning on student achievement in large courses are discussed. (Contains 4 tables and 1 figure.)