Serum samples from 64 apparently healthy individuals (32 men and 32 women, mean age 81.0 years) were examined for the prevalence of several autoantibodies, including rheumatoid factor (RF), antinuclear antibodies (ANA), antibodies to extracted cellular antigens Ro (SSA), La (SSB), Sm, U1nRNP and Scl-70. IgG and IgM isotype-specific ELISA methods were applied for the detection of antibodies to ssDNA (anti-ssDNA), to dsDNA (anti-dsDNA) and to cardiolipin (anti-CL). The sera of this elderly population were found to contain a plethora of autoantibodies; RF was detected in 14.1%, ANA in 31.3% and anti-Ro (SSA) in 1.6% of the individuals. Precipitating antibodies to La (SSB), Sm, U1nRNP and Scl-70 were absent, while 15.6% of the sera displayed precipitating antibodies to a common undefined human spleen antigen. ELISA methods revealed anti-ssDNA in 17.2% of the individuals, anti-dsDNA in 14.1% and anti-CL in an extremely high incidence (51.6%). Notably, the above autoantibodies were exclusively of IgG isotype. Tests of 261 sera from healthy non-elderly individuals disclosed only anti-CL (IgG and IgM isotypes) in 2.3% of them. The levels of IgA and IgG immunoglobulins were increased in 23.4% and 29.7% of the elderly subjects, respectively. IgM was elevated in 3.1%, but it was also found decreased in 9.4%. This study documents the high incidence of autoantibodies in the healthy elderly, including for the first time, anti-CL antibodies. Furthermore, the relative impairment in IgM autoantibody production observed, possibly indicates the involution of the senescent immune system.