Excessive thyroid hormone replacement carries the potential for serious long-term metabolic complications (e.g., accelerated osteoporosis). The increased bioavailability of commercially available products, along with improved laboratory assays for measuring thyrotropin (TSH), has led to an increased chance of actual or detected iatrogenic hyperthyroxinemia. The purpose of this study was to determine the frequency of excessive prescribing and to examine the impact of changes in potency of replacement thyroid hormone formulations and sensitivity of thyroid function tests on its incidence. A retrospective chart review was done of patients requiring thyroid hormone replacement therapy treated at a university-based, family medicine residency training program. The following information was extracted from each chart: specific thyroid medication (including dose and date of onset of therapy) and thyroid laboratory tests results (including serum thyroxine [T4] and TSH). This information from two different time periods (1975 to 1981 and 1982 to 1989) was compared using one-way analysis of variance. Serum T4 levels were not significantly different between the two time periods, 1975 to 1981 and 1982 to 1989 (8.06 +/- 2.93 micrograms/dl versus 9.0 +/- 03.69 micrograms/dl; NS), despite significant changes in TS serum levels (23.6 +/- 38.9 mIU/mL versus 7.44 +/- 18.7 mIU/ml; P = 0.009) and levothyroxine dosage (184 +/- 59.6 micrograms/d versus 145 +/- 64.1 micrograms/d; P = 0.002). Significantly more patients had low (supersuppressed) TSH levels between 1982 and 1990 than between 1975 and 1981 (33 percent versus 10 percent; P = 0.02.) Excessive thyroid hormone replacement with iatrogenic hyperthyroxinemia is a common occurrence. Clinicians need to be aware of this problem and implement measures (e.g., periodic monitoring of TSH) to minimize the occurrence of overdosing and the potential for long-term complications.