This study compared students' investigations with an atomic force microscope and viruses in real-time synchronous and asynchronous learning environments. Student interactions with scientists (live videoconference versus email) were examined to see whether communication patterns were different for the different modes of instruction. Students' knowledge of viruses, microscopy, and nanoscale science was compared for asynchronous (n = 44) and synchronous treatments (n = 41). Eight teams of four students were video-recorded and student discourse was analyzed. Data sources included students' questions, pre-instruction and post-instruction knowledge assessments, and written descriptions of the investigations. Results showed that students in the asynchronous group asked significantly more inquiry and interpretation questions of scientists and fewer questions about the scientists than students in the synchronous group. Both groups showed significant gains in knowledge of virus types and morphology. Students in the asynchronous group made significantly more written notations about what they learned from the investigations than students in the synchronous group. (Contains 6 tables.)