The main goal of this study was to explore whether the use of multimedia in genetics instruction contributes more to students' knowledge and comprehension than other instructional modes. We were also concerned with the influence of different instructional modes on the retention of knowledge and comprehension. In a quasi-experimental design, four comparable groups of 3rd and 4th grade high school students were taught the process of protein synthesis: group 1 was taught in the traditional lecture format (n = 112 students), group 2 only by reading text (n = 124 students), group 3 through multimedia that integrated two short computer animations (n = 115 students) and group 4 by text supplemented with illustrations (n = 117 students). All students received one pre-test in order to estimate their prior knowledge, and two post-tests in order to assess knowledge and comprehension immediately after learning and again after 5 weeks. Results showed that students comprising groups 3 and 4 acquired better knowledge and improved comprehension skills than the other two groups. Similar results were observed for retention of acquired knowledge and improved comprehension. These findings lead to the conclusion that better learning outcomes can be obtained by the use of animations or at least illustrations when learning genetics.