This study explored and documented the frequencies of conceptual difficulties confronted by college students seeking to understand the basic processes of cellular respiration. Using concept maps, clinical interviews and an open-ended instrument, viewpoints were elicited from 100 (novice) introductory biology students before and after relevant instruction in cellular respiration and from 100 (experienced) students enrolled in advanced biology courses. Chi-square analyses revealed significant differences among groups in the frequencies of scientifically acceptable and alternative conceptions. The findings suggest that novices harbor a wide range of conceptual difficulties that constrain their understanding of cellular respiration. Furthermore, many of these difficulties persist after instruction and new ones arise. Often these conceptual problems remain intact among experienced students despite well-planned, repeated instruction at advanced levels.