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In the context of hybrid instruction, this study was designed to explore whether gender has an influence on learners' preferences for synchronous or asynchronous modes of computer-mediated communication, and whether this decision impacts learners' self-efficacy (SE) towards knowledge acquisition. The participants were 180 teacher-education students (151 females and 29 males) enrolled in a hybrid (blend of traditional classroom instruction and online learning activities) foundations course at a United States research university with a proportionally high percentage of full-time commuters and/or distance enrolees. The findings showed that, regardless of gender, two-thirds of the participants preferred asynchronous modes over synchronous ones. In addition, gender was weakly related to the participants' SE in both modes. Linear regression indicated that SE, in turn, was weakly related to academic performance. The implications of these findings for instructional practice are discussed.