For the current study, we developed and tested a biopsychological model to combine research on psychological tension, the Limited Capacity Model of Motivated Mediated Message Processing, and the endocrine system to predict and understand how people process anti-drug PSAs. We predicted that co-presentation of pleasant and unpleasant information, vs. solely pleasant or unpleasant, will trigger evaluative tension about the target behavior in persuasive messages and result in a biological response (increase in cortisol, alpha amylase, and heart rate). In experiment 1, we assessed the impact of co-presentation of pleasant and unpleasant information in persuasive messages on evaluative tension (conceptualized as attitude ambivalence), in experiment 2, we explored the impact of co-presentation on endocrine system responses (salivary cortisol and alpha amylase), and in experiment 3, we assessed the impact of co-presentation on heart rate. Across all experiments, we demonstrated that co-presentation of pleasant and unpleasant information, vs. solely pleasant or unpleasant, in persuasive communications leads to increases in attitude ambivalence, salivary cortisol, salivary alpha amylase, and heart rate. Taken together, the results support the initial paths of our biopsychological model of persuasive message processing and indicate that including both pleasant and unpleasant information in a message impacts the viewer. We predict that increases in evaluative tension and biological responses will aid in memory and cognitive processing of the message. However, future research is needed to test that hypothesis.