The stress inoculation paradigm (SI), which consists of education (Ed), coping skills training (CS), and exposure to simulated stressors (Ex), was applied to the occupational stress experienced by nurses. Occupational stress was operationally defined in terms of 13 dependent measures reflecting problem areas summarized by the acronym Re ACT (retrograde complaints, assertiveness deficits, competency concerns, and time stress). ReACT also stood for the ingredients of the CS component (relaxation training, assertive skill building, cognitive restructuring, and time management instruction). In order to determine which SI components produce a treatment effect, 60 acute-care registered nurses were randomly assigned to one of four active treatment cells, namely, SI, CS, Ex, Ed, or no treatment at all (NT). A multivariate analysis of variance at posttest, and subsequent univariate analyses simultaneously considering 4-month follow-up data, clearly demonstrate that SI is an effective treatment with durable benefits and that CS is its principal ingredient. Additional demand-characteristics analyses indicate that these effects cannot likely be ascribed to placebo-related phenomena.