We measured in vitro mitogen responses, delayed hypersensitivity skin tests, circulating immune complexes (CIC) and three autoantibodies in 279 healthy and 24 chronically ill individuals over 65, and in young controls. The elderly individuals had previously undergone a complete medical examination and laboratory screening tests, and were on no medications. Compared to the results of 180 young controls tested concurrently, the healthy elderly individuals had significantly depressed PHA responses and skin test responses. In addition, CIC and autoantibodies were increased in the healthy elderly group compared to young controls. There was no difference in PHA or skin test responses between the healthy and chronically ill elderly subjects, suggesting that the major determinant of depressed cellular immunity in the elderly is age per se and not age-associated diseases. Within the elderly population, aged 65-94, there was a significant decrease in PHA response with age. Previously it has been reported that correlations exist between measurements of cellular immune response (mitogen response and skin testing) and manifestations of autoimmunity (CIC or autoantibodies) in elderly subjects. However, in this well characterized healthy elderly population we could not verify an association between the cellular immune response and either autoantibodies or immune complexes. In addition, was no increased prevalence of autoantibodies in subjects with CIC.