Very few data have been reported on the frequency of autoantibodies (AAs) in normal children. In the present study we investigated the frequency of 14 AAs in a total of 268 apparently normal children (151 boys and 117 girls; age range, 1 month to 14 years). Forty-one children (22 boys and 19 girls) were positive for at least one AA, usually in a low titer; two children were positive for two AAs. None of these children had a personal or family history of autoimmune diseases. The percentage of children positive for each AA was as follows: antinuclear, 3%; anti-smooth muscle, 2.6%; antireticulin, 2.6%; antimitochondrial, 1.1%; rheumatoid factor, 0.6%; antiribosomal, 0.4%; anti-gastric parietal cells, 5.2%; and anti-thyroid microsomal, 1.3%. Anti-double-stranded DNA, anti-intestinal epithelial cells, antiliver and antikidney microsomal, antithyroglobulin, anti-islet cells, and complement-fixing anti-islet cell antibodies were not detected in any serum. Fifteen of the 41 positive children were checked for the presence of AAs two years later; six (40%) were still positive, always for the same AA, without major differences in titer. Our results suggest that the overall frequency of AAs in apparently healthy children is quite similar to that reported in young adults; this AA positivity seems most often to represent a transient phenomenon.