This study deals with the effect of chronic stress on physiological responsiveness to an acute psychological stressor in male high school teachers. Chronic stress was operationalized as the self-reported number of everyday problems. Twenty-seven subjects reporting extremely low or high numbers of everyday problems were exposed to an acute psychological stressor, and changes in immunologic, endocrine, and cardiovascular parameters were monitored. The stressor included a learning process followed by a teaching session in which a confederate to the researchers was involved. Twenty subjects served as controls. The stressor had no effect on the endocrine variables measured but induced increases in heart rate and blood pressure, which were similar in both chronic stress groups. Analysis of subsets of blood lymphocytes revealed differences in natural killer (NK) and T cell responses in the low and the high stress groups. It is concluded that 1) immunologic responsiveness to an acute psychological stressor is related to problems experienced in daily life, and that 2) chronic stress differentially modifies the sensitivity of biological systems to mild acute stressors.