Objective: To examine the effects of 17-wk physical exercise and enriched foods on cellular immune response (CIR) in frail elderly. Methods: A total of 112 independently living, frail elderly men and women (mean age 79.2 +/- 5.9) received: twice weekly comprehensive, moderate intensity, progressive group exercise (group A, N = 26); daily enriched foods (group B, N = 31); both (group C, N = 29); or neither (group D, N = 26). Exercises focused on skills training. Foods were enriched with micronutrients with a high prevalence of deficiency in older people (at 25-100% the RDA). A social program and identical regular foods were offered as a control. CIR was measured by delayed-type hypersensitivity skin test response (DTH) against seven recall antigens expressed as the total number of positive responses and sum of diameters of all positive responses. Results: No independent or interactive effect of enriched foods was observed. Therefore, exercise (groups A + C) was compared with no exercise (groups B + D). Nonexercising subjects showed an average decline of 0.5 responses compared with an unchanged responsiveness among exercising subjects (difference = 0.5, 95% CI: 0.04-0.89, P = 0.03 adjusted for baseline DTH, activity level, and micronutrient status). Nonexercising subjects had a larger decline in the sum of diameters of all positive responses than exercising subjects but the difference did not reach significance (adjusted difference = 2.1 mm, 95% CI:-1.0-4.8). Conclusion: Exercise may prevent or slow the age-related decline in immune response. Micronutrient enriched foods showed no effect. As infectious diseases can have debilitating or even fatal consequences for the elderly, prevention of the age-related decline in CIR could significantly improve their quality of life.