The authors tested the predictions of a game theory model of plagiarism, using a test population of student papers submitted to an online plagiarism detection program, over five semesters in a non-majors biology course with multiple sections and high enrollment. Consistent with the model, as the probability of detection and the penalty if caught increased, plagiarism rates dropped, although the latter had a smaller effect. The percentage of plagiarized papers decreased from almost 30% to less than 6% between semesters, as more students became aware that the entire course utilizes a plagiarism detection program and penalizes students who are caught plagiarizing. (Contains 1 table and 5 figures.)