Increased vagal tone has been associated with treatment success using pharmacological agents and cognitive-behavioral treatment in major depression, but not using electroconvulsive therapy. The present study investigated whether increases in vagal tone would be associated with favorable treatment response with nonpharmacological treatment. At baseline and following treatment, 16 subjects were administered the Hamilton Rating Scale for Depression (HRSD) followed by electrocardiographic recording. Those with little change in vagal tone from before to after treatment showed minimal reduction in HRSD score (−4.8); those with larger vagal tone change showed a large decrease in HRSD score (−14.8). Changes in vagal tone are thus related to favorable treatment response in depression, and do not represent anticholinergic pharmacological effects. Future work manipulating vagal tone might prove informative in teasing apart the causal role of vagal tone and depression.