Seven female patients (mean age 86 years) with proven biochemical primary hypothyroidism were enrolled in a single-blind randomized crossover study, of standard daily versus twice-weekly thyroxine therapy, with each phase of one month's duration. The median daily dose of thyroxine was 100 micrograms (range 75-100 micrograms). Serum levels of thyroid hormones and thyrotrophin were very similar during twice-weekly thyroxine therapy to those during daily therapy and there were no statistically significant differences between trough and peak serum total triiodothyronine, free thyroxine, or thyrotrophin levels or systolic time intervals during twice-weekly thyroxine. Administration of thyroxine twice-weekly to elderly patients with primary hypothyroidism gives effective biochemical thyroid hormone replacement, with no evidence from the systolic time intervals of tissue thyrotoxicosis at expected peak thyroid hormone concentrations. Supervised twice-weekly thyroxine should be considered in patients with primary hypothyroidism who comply poorly with daily dosing.