Active investigative student-directed experiences in laboratory science are being encouraged by national science organizations. A growing body of evidence from classroom assessment supports their effectiveness. This study describes four years of implementation and assessment of an investigative laboratory course in human physiology for 65 second-year students in sports medicine and biology at a small private comprehensive college. The course builds on skills and abilities first introduced in an introductory investigations course and introduces additional higher-level skills and more complex human experimental models. In four multiweek experimental modules, involving neuromuscular, reflex, and cardiovascular physiology, by use of computerized hardware/software with a variety of transducers, students carry out self-designed experiments with human subjects and perform data collection and analysis, collaborative writing, and peer editing. In assessments, including standard course evaluations and the Salgains Web-based evaluation, student responses to this approach are enthusiastic, and gains in their skills and abilities are evident in their comments and in improved performance.