OBJECTIVES To test a brief, non-sectarian program of meditation training for effects on perceived stress and negative emotion, and to determine effects of practice frequency and test the moderating effects of neuroticism (emotional lability) on treatment outcome. DESIGN AND SETTING The study used a single-group, open-label, pre-test post-test design conducted in the setting of a university medical center. PARTICIPANTS Healthy adults (N=200) interested in learning meditation for stress-reduction were enrolled. One hundred thirty-three (76% females) completed at least 1 follow-up visit and were included in data analyses. INTERVENTION Participants learned a simple mantra-based meditation technique in 4, 1-hour small-group meetings, with instructions to practice for 15-20 minutes twice daily. Instruction was based on a psychophysiological model of meditation practice and its expected effects on stress. OUTCOME MEASURES Baseline and monthly follow-up measures of Profile of Mood States; Perceived Stress Scale; State-Trait Anxiety Inventory (STAI); and Brief Symptom Inventory (BSI). Practice frequency was indexed by monthly retrospective ratings. Neuroticism was evaluated as a potential moderator of treatment effects. RESULTS All 4 outcome measures improved significantly after instruction, with reductions from baseline that ranged from 14% (STAI) to 36% (BSI). More frequent practice was associated with better outcome. Higher baseline neuroticism scores were associated with greater improvement. CONCLUSIONS Preliminary evidence suggests that even brief instruction in a simple meditation technique can improve negative mood and perceived stress in healthy adults, which could yield long-term health benefits. Frequency of practice does affect outcome. Those most likely to experience negative emotions may benefit the most from the intervention.