Self-determination theory was applied to explore the motivational basis of adherence to long-term medication prescriptions. Adult outpatients with various diagnoses who had been on a medication for at least 1 month and expected to continue (a) completed questionnaires that assessed their autonomous regulation, other motivation variables, and perceptions of their physicians' support of their autonomy by hearing their concerns and offering choice; (b) provided subjective ratings of their adherence and a 2-day retrospective pill count during an interview with a clinical psychologist; and (c) provided a 14-day prospective pill count during a subsequent, brief telephone survey. LISREL analyses supported the self-determination model for adherence by confirming that patients' autonomous motivation for adherence did mediate the relation between patients' perceptions of their physicians' autonomy support and their own medication adherence.