We undertook this study to identify persons with high medical use to target them for health promotion and self-management interventions specific to their problems. We compared the reductions in cost and health risk of a health education program aimed at high-risk persons with a similar program addressed to all risk levels. We compared health risk and use in 2,586 high-risk persons with those of employee (N = 50,576) and senior (N = 39,076) groups and contrasted results in specific high-risk disease or behavior categories (modules)--arthritis, back pain, high blood pressure, diabetes mellitus, heart disease, smoking, and obesity--against each other, using validated self-report measures, over a 6-month period. Interventions were a standard generic health education program and a similar program directed at high risk individuals (Healthtrac). Health risk scores improved by 11% in the overall high-risk group compared with 9% in the employee group and 6% in the senior group. Physician use decreased by 0.8 visits per 6 months in the high-risk group compared with 0.05 and 0.15 visits, respectively, per 6 months in the employee and senior groups. Hospital stays decreased by 0.2 days per 6 months in the high-risk group compared with 0.05 days in the comparison groups. The duration of illness or confinement to home decreased by 0.9 days per 6 months in the high-risk group and 0.15 and 0.25, respectively, in the employee and senior groups. Using imputed costs of $130 per physician visit, $1,000 per hospital day, and $200 per sick day, previous year costs were $1,138 in direct costs for the high-risk groups compared with $352 and $995 in the employee and senior groups, respectively. At 6 months, direct costs were reduced by $304 in the high-risk group compared with $57 and $70 in the comparison groups. Total costs were reduced $484 in the high-risk groups compared with $87 in the employee group and $120 in the senior group. The return on investment was about 6:1 in the high-risk group compared with 4:1 in the comparison groups. Effective health education programs can result in larger changes in use and costs in high-risk persons than in unscreened persons, justifying more intensive educational interventions in high-risk groups.