Isolated elevations of basal TSH levels are frequently observed in the general population. In a prospective study we analyzed the spontaneous evolution of thyroid function over time in such patients. The mean observation period was 5.4 (0.5-12) years. During the follow-up period 20% of these patients developed overt hypothyroidism. The risk of developing hypothyroidism was determined primarily by the initial TSH value and an additive effect was found for the thyroid antibodies and the thyroidal reserve (delta-T3) after TRH stimulation (Cox proportional hazard model). The cumulative risk for overt hypothyroidism after 10 years was only 22% for a mean TSH level of 12 mU/l for patients with negative thyroid antibodies and a good thyroidal reserve (low-risk), but increased to 63% for patients with positive antibodies and impaired T3 reserve (high-risk). Therefore, patients with isolated elevation of TSH can be divided into two subgroups according to the results of TSH, antibody status and T3 reserve: (1) In the "low-risk group" with good prognostic factors the patients should be followed up by periodic laboratory testing only (TSH, FT4, every 2-3 years). (2) In the "high-risk group" with clearly abnormal parameters, however, frequent controls are mandatory (every 6-12 months) or treatment with thyroxine may be indicated.