Our objective was to identify endocrine-related mechanisms capable of mediating preventive effects of stress reduction in hypertensive heart disease. Since beneficial effects of stress reduction accrue over time, this cross-sectional, descriptive study sought differences between healthy students not practicing a systematic technique for reducing stress (the average stress, or AS, group, n = 33) and a similar group who for 8.5 years had practiced the Transcendental Meditation (TM) technique, used widely to reduce stress (the low stress, or LS, group, n = 22). The two groups of students, matched for age and area of study, performed timed collections of urine that included (separately) the entire waking and sleeping portions of 1 day. They also completed the Profile of Mood States and the State-Trait Anxiety Inventory, self-report instruments sensitive to subjective level of stress. Urine samples were analyzed for adrenocortical steroids by radioimmunoassay, for Na+, K+, Mg2+, Ca2+, and Zn2+ by atomic absorption spectrometry, and for neurotransmitter metabolites by reverse-phase, high-performance, liquid chromatography, and spectrophotometry. The two groups differed significantly on most measures. Specifically, the LS group was lower in cortisol and aldosterone and higher in dehydroepiandrosterone sulfate (DS) and the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA). Excretion of sodium, calcium, zinc, and the norepinephrine metabolite, vanillylmandelic acid (VMA), was also lower in this group, as were Na+/K+ ratio, mood disturbance, and anxiety. In women practicing TM, cortisol correlated inversely and DS directly with number of months of TM practice. The results identify improvements in mood state, adrenocortical activity, and kidney function as probable factors in the preventive and treatment effects of stress reduction. Because suboptimal levels of these parameters result from chronic, subjective stress, the findings add mechanistic support to the contention that hypertensive heart disease is avoidable, even in modern industrialized societies.