OBJECTIVES: To determine whether a 15-minute, one-time guided relaxation program for cancer patients could improve symptom distress as measured by the Edmonton Symptom Assessment System (ESAS). In addition, we were interested in characterizing the changes of the autonomic nervous system, as demonstrated by heart rate variability (HRV) high-frequency (HF) spectral analysis, before and after this relaxation program. DESIGN: Nonrandomized pilot study. SETTING: Comprehensive cancer center. METHODS: Twenty cancer patients underwent a 15-minute relaxation program. The ESAS and a 5-minute HRV recording were completed before and after the relaxation program. MAIN OUTCOME MEASURES: The differences between the pre- and post-summed ESAS score and HRV values were compared by a paired t-test. RESULTS: The summed ESAS scores were significantly lower after the relaxation program (P<.01), with an average 31% decrease in total score. However, no differences were found in HRV HF power. There was no correlation between the change in HRV HF and change in symptom distress, as measured by ESAS. CONCLUSIONS: A brief guided relaxation program can significantly improve symptoms as measured by ESAS. More research is required to understand the effects of relaxation on HF HRV power.