Procollagen (I) carboxyterminal propeptide (PICP) is a metabolite of procollagen, a precursor molecule of collagen type I, which accounts for more than 90% of the organic matrix of the bones. Serum PICP levels indicate the rate of bone collagen synthesis and therefore the osteoblastic activity. In this study we evaluate the clinical usefulness of serum PICP as an indicator of bone metastases in patients with prostate cancer in relation to bone scan and to prostate specific antigen (PSA) measurements. We found no similar study in the literature relating these three tests. Seventy-eight patients (median age 63+/-4,3 years) with prostate adenocarcinoma were examined. The diagnosis was confirmed histologically. Bone metastases were diagnosed in 42 (54%) of them assessed by bone scans (Group A), while the remaining 36 patients (46%) had no bone metastases (negative bone scans and X-rays) (Group B). We also examined 21 patients with benign prostate hyperplasia as a control group (Group C). All patients had serum PICP measurements, bone scans with (99m)Tc-MDP and PSA measurements. None of them had a history of disease or of using drugs known to affect bone metabolism. Serum levels of PICP were assayed by a radioimmunoassay (RIA) kit (Orion Cooperation, Farmos Diagnostics, Finland). Serum PSA was also tested by a RIA kit (Tandem-R, Hybritech Inc, USA). PICP levels in Group A were 265+/-89 microg/l, in Group B 128+/-39 microg/l and in Group C patients 110+/-48 microg/l. High levels of PICP above 170 microg/l, were diagnostic of bone metastases with sensitivity 54%, specificity 93% and accuracy 84%. In comparison, PSA levels above 4 ng/ml were also diagnostic with a sensitivity of 68%, specificity of 91% and accuracy 88%. Patients with low levels of PICP, lower than 90 microg/l, n=31, had no bone metastases. The positive prognostic value of bone scan was 74% with a sensitivity of 76%, specificity of 58% and accuracy 71%. Positive bone scans combined with very high levels of PICP and PSA, had positive prognostic value 97%, with sensitivity of 78%, specificity of 96% and accuracy 97%, while bone scans with levels of PICP lower than 170 microg/l, had positive prognostic value of 32%. Levels of PICP and PSA were significantly higher in patients with prostate cancer and bone metastases in comparison to patients with benign prostate hyperplasia (P<0.0001) respectively. Also, levels of PICP and PSA were higher in patients with prostate cancer without metastases as compared to prostate hyperplasia (P<0.0005 and P<0.0001 respectively) (Wilcoxon-Mann-Whitney test). When metastases were more extensive, PICP levels were higher than PSA. It is concluded that PICP as a marker of osteoblastic activity is useful for diagnosing bone metastases of prostate adenocarcinoma but when co-evaluated with PSA and the bone scan, the diagnostic accuracy of these three diagnostic procedures is much higher.