This study investigated different ways in which work stressors, sense of coherence (SOC), and negative affectivity (NA) might influence strain. Three models covering direct, moderating, and mediating effects between the variables were tested for hyperresponsitivity, causality, perception, selection, and stressor-creation mechanisms. The sample consisted of 205 hospital employees (nurses, physicians, and medical technicians). Work stressors, SOC, NA, and strain were measured and analyzed in structural equation models and with analyses of variance. Besides direct effects on strain, significant perception, selection, and stressor-creation mechanisms of SOC could be identified. After controlling for SOC and NA, work stressors remain substantial predictors of strain.