There are several indications that the functions of human osteoblasts and osteoclasts have circadian rhythms with peak activities occurring at night. It is not known, however, whether the principal function of these cells, namely synthesis and degradation of the organic matrix of bone, of which about 90% is type I collagen, also has a circadian rhythm. This was therefore investigated for both the formation of type I collagen and the degradation of type I collagen in bone using two newly developed serum markers: the serum concentration of the carboxy-terminal propeptide of type I procollagen (PICP) as a marker of formation and the serum concentration of the carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) as a marker of degradation. PICP and ICTP were measured by RIA in samples taken every 3 h over a 24 h period in 12 healthy premenopausal women (age 32 +/- 5 years, mean +/- SD). Both PICP (p = 0.003) and ICTP (p = 0.00003) showed a significant circadian rhythm, with about 20% higher values at night than in the afternoon. We conclude that serum markers of both the formation of new type I collagen and the degradation of old type I collagen in bone exhibit a clear circadian rhythm, with increased activity of both osteoblasts and osteoclasts at night. The etiology of this circadian rhythm is still unknown.