Controversy persists about the role of subclinical hypothyroidism in hypercholesterolemia. This study aimed to assess in a clinically healthy, middle-aged population of employees the prevalence of thyroid function disorders and their relation to demographic variables and cardiovascular risk factors. 1922 (former) employees were screened with follow-up of newly identified cases of undiagnosed (subclinical) hypothyroidism and hyperthyroidism. Thyroid stimulating hormone (TSH), prevalence and course of (subclinical) hypo- and hyperthyroidism and their relation to cardiovascular risk factors (cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, smoking, systolic and diastolic blood pressure) were assessed. The prevalence of newly diagnosed subclinical hypothyroidism (cut-off TSH concentration: 4.0 mU/L) was 1.1% (17 women and 5 men) with a mean TSH concentration of 7.37 (95% CI 5.18-9.56) mU/L. No case of overt hypothyroidism could be diagnosed. Elevated levels of antibodies to microsomal or thyroglobulin antigens were detected in six subjects with subclinical hypothyroidism (27.3%). Fifteen subjects (0.8%, 13 women and 2 men) had TSH concentrations below 0.1 mU/L. The cardiovascular risk profile of subjects with mild subclinical hypothyroidism was not different from subjects with normal TSH levels. The prevalence of subclinical hypothyroidism was 0.8% in normocholesterolemic (cholesterol <5.2 mmol/l) and 1.4% in hypercholesterolemic subjects (n.s.). One woman each with the subclinical form of the disease developed hypothyroidism or hyperthyroidism after 21 and 11 months of follow-up, respectively. Subclinical hypothyroidism and subclinical hyperthyroidism were rarely observed in a target group for coronary heart disease prevention. Mild subclinical hypothyroidism was not associated with any adverse cardiovascular risk profile. These results argue against indiscriminate measurements of TSH concentrations in clinically healthy subjects either with normocholesterolemia or hypercholesterolemia.