A 63-year-old female exhibited primary hypothyroidism, both upon clinical examination and laboratory tests. A full neuropsychological exam and repeated, multiple measures of affect, memory, concentration, and problem solving were used to establish baselines prior to treatment and to assess change during the first 7 months of thyroid hormone replacement therapy. Additionally, thyroid hormone and metabolites T3, T4, TSH, and T3 (resin uptake) were regularly assessed. Results indicated that establishing stable baselines before treatment, long-term repeated assessments during treatment, and the use of control subjects are crucial to understanding the neuropsychological changes associated with hypothyroidism. Certain measures of depression, anxiety, attention, and concentration changed from severely impaired to normal levels following an explanation of the diagnosis but before actual treatment. Baseline memory functions were impaired before treatment and remained impaired relative to normals during replacement therapy in spite of improvement with repeated testing. However, replacement therapy may have arrested the progression of memory deterioration as no further decline was evident at a 7-month follow-up. Our data suggest that the memory changes associated with primary hypothyroidism may not be reversed by thyroid hormone replacement therapy.