Stress-reduction interventions have been linked with enhanced well-being and health. This study examined affect and cortisol in 111 individuals randomly assigned to a single 35-minute guided relaxation or a stress management lecture control group. Positive affect increased more in the relaxation compared to the control group (F = 6.62, p = .01). Dispositional stress reactivity had a moderating influence (R² = .248, p < .001), such that individuals high in stress reactivity showed highest increases in positive affect to the relaxation. Results indicate that a single guided relaxation intervention improves positive affect among individuals high in stress reactivity.