This study addressed the effects of a naturally occurring stressor on components of the immune response. Blood was drawn twice from 75 first-year medical students, with a baseline sample taken one month before their final examinations and a stress sample drawn on the first day of final examinations. Median splits on scores from the Holmes—Rahe Social Readjustment Rating Scale and the UCLA Loneliness Scale produced a 2 X 2 X 2 repeated measures ANOVA when combined with the trials variable. Natural killer (NK) cell activity declined significantly from the first to the second sample. High scorers on stressful life events and loneliness had significantly lower levels of NK activity. Total plasma IgA increased significantly from the first to second sample, while plasma IgG and IgM, C-reactive protein, and salivary IgA did not change significantly.