We investigated the influence of L-thyroxine (L-T-4) treatment over 3 weeks on biochemical markers of bone turnover in 12 healthy young men (age 25.6 +/- 1.4 years, BMI: 22.6 +/- 2.5 kg/m(2)). Serum parameters indicating bone formation [bone Gla protein (BGP), carboxyterminal propeptide of type I procollagen (PICP), and bone-specific alkaline phosphatase (BAP)] and bone resorption [cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and the urinary excretion of pyridinoline (Pyr) and deoxypyridinoline (D-Pyr)] were measured before and after three weeks of treatment with 300 mu g LT(4)/d, T-3 and T-4 significantly increased and TSH decreased to almost undetectable levels even when measured with a third generation TSH assay. Markers of bone formation showed variable responses with a small but significant increase in BGP but not in PICP or BAP. In contrast, all parameters of bone resorption increased significantly with a good correlation between D-Pyr excretion and the serum parameter ICTP (r = 0.78, p < 0.0001). These changes in bone-turnover markers were not necessarily paralleled by comparable increments of other markers of tissue thyrotoxicosis (SHBG, pulse rate, VO2), suggesting a variability in tissue sensitivity. These rapid responding parameters, especially in the easily obtainable serum parameter ICTP, might be valuable tools in the evaluation of several states of thyroxine excess.