The primary purpose of the present study was to compare the effectiveness of two collaborative grouping strategies and two instructional methods in terms of gains in reasoning ability and achievement in college biology. In order to do so, a quasi-experimental study was performed in which students were placed in one of four treatment conditions: heterogeneous grouping within inquiry instruction, homogeneous grouping within inquiry instruction, heterogeneous grouping within non-inquiry instruction, and homogeneous grouping within non-inquiry instruction. Students were placed in groups based on initial reasoning level. Reasoning levels and achievement gains were assessed at the end of the study. Results showed that within non-inquiry instruction, heterogeneous mean group scores were higher in both reasoning and achievement than homogeneous groups. In contrast, within inquiry instruction, homogeneous mean group scores were higher in both reasoning and achievement. Inquiry instruction, as a whole, significantly outperformed non-inquiry instruction in the development of reasoning ability. Within inquiry instruction, low-ability students had significantly greater reasoning gains when grouped homogeneously. These results support Piaget's developmental theory and contradict Vygotsky's developmental theory. These results also suggest that the success of one grouping strategy over another is highly dependent upon the nature of instruction, which may be a cause for such conflicting views on grouping strategies within the educational literature. In addition, inquiry instruction led to students having greater confidence in their reasoning ability as well as a more positive attitude toward collaboration. Instructional implications are discussed.