Background: The aim of this study was to identify the aspects of cardiac physiology associated with depressive disorder early in life by examining measures of autonomic cardiac control in a community-based sample of depressed adolescents at an early phase of illness, and matched on a number of demographic factors with a non-depressed comparison group. Methods: Participants were 127 adolescents (44 boys), ages 14-18, who formed two demographically matched groups of clinically depressed and non-depressed participants. Adolescents were excluded if they evidenced comorbid externalizing or substance-dependence disorders, were taking medications with known cardiac effects, or reported regular nicotine use. Resting measures of heart rate, respiratory sinus arrhythmia, skin conductance level, blood pressure, and pre-ejection period were collected. Results: Depressed adolescents had resting heart rates significantly higher than those of healthy adolescents. No other measure of autonomic functioning differentiated the groups. Post-hoc analyses were conducted to examine the influence of illness chronicity, severity, comorbidity and sex on cardiac psychophysiology. These variables did not appear to exert a significant influence on the findings. Conclusions: Our findings suggest that neither autonomic cardiac control, illness chronicity or severity, nor medication effects fully explain resting heart rate differences between depressed and non-depressed adolescents. Future research on depression and heart rate should consider mechanisms other than sympathetic or parasympathetic control as potential explanations of heart rate differences, including blood-clotting mechanisms, vascular and endothelial dysfunction of the coronary arteries, and inflammatory immune system response.