Compassion is critical for societal wellbeing. Yet, it remains unclear how specific thoughts and feelings motivate compassionate behavior, and we lack a scientific understanding of how to effectively cultivate compassion. Here, we conducted 2 studies designed to a) develop a psychological model predicting compassionate behavior, and b) test this model as a mediator of a Compassion Meditation (CM) intervention and identify the “active ingredients” of CM. In Study 1, we developed a model predicting compassionate behavior, operationalized as real-money charitable donation, from a linear combination of self-reported tenderness, personal distress, perceived blamelessness, and perceived instrumental value of helping with high cross-validated accuracy, r=. 67, p<. 0001. Perceived similarity to suffering others did not predict charitable donation when controlling for other feelings and attributions. In Study 2, a randomized controlled trial, we tested the Study 1 model as a mediator of CM and investigated active ingredients. We compared a smartphone-based CM program to 2 conditions—placebo oxytocin and a Familiarity intervention—to control for expectancy effects, demand characteristics, and familiarity effects. Relative to control conditions, CM increased charitable donations, and changes in the Study 1 model of feelings and attributions mediated this effect (pab=. 002). The Familiarity intervention led to decreases in primary outcomes, while placebo oxytocin had no significant effects on primary outcomes. Overall, this work contributes a quantitative model of compassionate behavior, and informs our understanding of the change processes and intervention components of CM.(PsycInfo Database Record (c) 2020 APA, all rights reserved)