Using a double isotope method, the optimal conditions for the absorption of an L-thyroxine (L-T4) preparation were examined. In particular, the influence of food intake on L-T4 absorption was examined. As distinct from the unfavorable results hitherto obtained with L-T4 lactase mixtures, a tablet similar to a commercial 100 mug L-T4 lactose preparation showed good absorptionof 70.6% +/- 12.9% SD. In the fasting state, the L-T4 absorption of both preparations was significantly better (p less than 0.001) than with simultaneous food intake: 79.3% +/- 7.2% SD versus 63.9% +/- 10.5% SD. The calculated absorption of a 3-mg L-T4 dose in a lactose preparation used in testing thyroid suppressibility was significantly lower (p less than 0.001) than the absorption of a smaller L-T4 dose, and the absorption in the fasting state was again signifiantly (; less than 0.01) higher compared to that with simultaneous food intake: 52.6% +/- 4.3% SD versus 43.9% +/- 5.4% SD. The possibility of retention in the liver in the case of a large 3-mg L-T4 dose is indicated. The data suggest that with L-thyroxine medication simultaneous food intake should be avoided.