This study was performed to evaluate the prognostic significance of serum markers of bone and collagen metabolism in multiple myeloma. Serum C-terminal telopeptide of type I collagen (ICTP) reflects degradation of bone, whereas serum osteocalcin, together with serum C-terminal propeptide of procollagen type I (PICP) and serum bone-specific alkaline phosphatase (bAP) reflect synthesis of bone matrix. The N-terminal propeptide of procollagen type III (PIIINP) in serum reflects synthesis of type III collagen. We analysed frozen sera from 109 patients with newly diagnosed multiple myeloma. Serum ICTP was elevated (> 5.0 micrograms/l) in most patients (median 6.6 micrograms/l range 1.4-29.4 micrograms/l). Serum PIIINP was elevated (> 4.2 micrograms/l) in 46% (median 4.0 micrograms/l, range 1.4-20.1 micrograms/l). Serum PICP was generally within the reference limits, whereas serum osteocalcin and serum bAP were elevated in 19% and 37%, respectively. Serum ICTP correlated with serum PIIINP, serum beta 2-microglobulin (beta 2m), serum calcium, performance status, and stage. In univariate analysis, the test variables serum ICTP (P = 0.026) and serum osteocalcin (P = 0.036) were found to be of prognostic value, but PIIINP, PICP, or bAP in serum were not. Serum ICTP and serum beta 2m had a similar prognostic value. In multivariate analysis, serum calcium showed the highest prognostic significance, and serum beta 2m was the only other variable of independent prognostic value. However, in normocalcaemic patients, serum ICTP showed the highest prognostic significance, followed by serum osteocalcin. Thus, the serum levels of ICTP and osteocalcin seem related to bone turnover and calcium metabolism, and provide further information about myeloma activity, particularly in normocalcaemic patients.