This study investigated the effect of conceptual change instruction on Grade 11 students' (aged 16 - 17 years) understanding of respiration. To first determine students' misconceptions, ten Grade 11 students were interviewed and data obtained from these interviews and related literature was used to develop the Respiration Concept Test used in the next stage of the research. The test was administered to a total of 68 Grade 11 students in two classes of an urban high school. The experimental group consisted of 34 students, 18 boys and 16 girls, who received conceptual change instruction; the control group was made up of 34 students, 19 boys and 15 girls. The control group received traditional instruction in which the teacher provided instruction through lecture and discussion methods. Prior to instruction, students in both groups were pre-tested in order to determine their previous understanding of respiration. The results revealed that students in both groups had an equal understanding of respiration. After instruction, data were analysed with two-way analysis of covariance (ANCOVA) using science process skill scores as a covariate. Results indicated that students' science process skills accounted for a significant portion of variation in respiration concepts achievement. The conceptual change instruction, which explicitly dealt with students' misconceptions, produced significantly greater achievement in the understanding of respiration concepts. This analysis also revealed a significant difference between the performance of females and that of males in the favour of females, but there was no significant interaction between treatment and gender difference.