It has previously been shown that thyroid antibodies affect thyroid stimulating hormone (TSH) concentrations in men and women and that TSH levels are predictive of future thyroid disease. We investigated the validity of the National Academy of Clinical Biochemistry (NACB) guidelines regarding the TSH reference interval by studying 1512 individuals. Two hundred and fifty had at least one thyroid antibody, 121 were taking medications other than estrogens and occasional analgesics, and 105 reported a family history of thyroid disease. Serum TSH, thyroid peroxidase antibodies (TPOab) and thyroglobulin antibodies (Tgab) were determined on AutoDELFIA and TSHRab by a radioreceptor assay (RRA) from Brahms Diagnostica. For individuals without thyroid antibodies and other risk factors, no effect of age and gender was seen for serum TSH. Neither medication nor the presence of Tgab alone had any influence on serum TSH. TPOab alone or in combination with Tgab were associated with an increased serum TSH level. The 'cumulative percentage distributions' of subgroups, as well as the combined population, was In-Gaussian distributed. The central 95% of the population was within the 95% CI in rankit-plots. Consequently, a common reference interval for serum TSH of 0.58-4.07 mlU/l for all adults between 17 and 66 years of age was established. This reference interval is much higher than expected from the NACB-guidelines.