In this paper, the authors report some of the salient findings of a large-scale, four-year national study, conducted at the Harvard-Smithsonian Center for Astrophysics, entitled "Factors Influencing College Science Success" (FICSS), which surveyed college students who enrolled in first-year biology, chemistry, and physics courses throughout the United States. The purpose of the study is to compare and contrast the relative importance of two types of factors: (1) demographic/educational factors; and (2) high school experiential factors, that potentially affect achievement in science courses. The data were collected in 128 first-semester introductory college science courses taught in fall 2002 and fall 2003 at 55 four-year colleges and universities located in 34 states. Using a regression analysis that seeks to find the linear combination of weighted independent variables(demographic/educational and experiential factors) that explains as much variation in some dependent measure (final course grade), the findings reveal that approximately 21-22% of variation in final course grades can be explained by a combination of demographic/educational and high school experiential factors, and another 13% is explained by differences in grading policies and practices among colleges and universities. This analysis of representative college students from across the United States offers a strong case that students approach science teachers with a diverse set of preexisting factors that strongly influence their success in college science courses. (Contains 3 tables.)