This study examined the science process skill of prediction problem solving using naturalistic research methodology and information-processing theory. The think-aloud interview led to the identification of several specific program exploration and prediction behaviors. A total of 14 high school biology students made predictions concerning the effects of the independent variables upon dependent variables through time using a computer simulation on water pollution. Students were identified according to initial knowledge of the subject matter and success at solving three selected prediction problems. Successful predictors generally had high initial knowledge of the subject matter and were formal. Unsuccessful predictors generally had low initial knowledge of the subject matter and were concrete. High initial knowledge seemed to be more important to predictive success than stage of Piagetian cognitive development. Behavioral tendencies between successful and unsuccessful predictors over all stages of the learning sequence and between stage one and stage three predictions were compared. Implications for problem-solving theory, cognitive development, and science teaching were discussed. (Author/YP)