This study employed problem-based learning for project work in a year 9 biology class. The purpose of the study was to investigate (a) students' inspirations for their self-generated problems and questions, (b) the kinds of questions that students asked individually and collaboratively, and (c) how students' questions guided them in knowledge construction. Data sources included observation and field notes, students' written documents, audiotapes and videotapes of students working in groups, and student interviews. Sources of inspiration for students' problems and questions included cultural beliefs and folklore; wonderment about information propagated by advertisements and the media; curiosity arising from personal encounters, family members' concerns, or observations of others; and issues arising from previous lessons in the school curriculum. Questions asked individually pertained to validation of common beliefs and misconceptions, basic information, explanations, and imagined scenarios. The findings regarding questions asked collaboratively are presented as two assertions. Assertion 1 maintained that students' course of learning were driven by their questions. Assertion 2 was that the ability to ask the “right'' questions and the extent to which these could be answered, were important in sustaining students' interest in the project. Implications of the findings for instructional practice are discussed. © 2004 Wiley Periodicals, Inc. Sci Ed88:707–727, 2004