Insulinlike growth factor 1 (IGF-1) has growth-promoting effects on myeloma cells in vitro as well as in vivo. In this study, we measured the concentration of IGF-1 and its major binding protein, IGF- binding protein 3 (IGFBP-3), in serum from 127 patients with multiple myeloma. Serum had been drawn at the time of diagnosis, before treatment with high-dose melphalan. IGFBP-3 in myeloma patients (1.6 +/- 0.73 microg/mL; mean +/- SD) was significantly decreased compared to healthy age- and sex-matched controls (2.2 +/- 0.42 microg/mL). However, IGFBP-3 had no prognostic value in this study. The mean IGF-1 level did not differ between myeloma patients (17.8 +/- 7.7 nM) and controls (17.3 +/- 5.6 nM). Nevertheless, IGF-1 was a strong indicator of prognosis. After 80 months of follow-up, myeloma patients with low levels (< 13 nM) of serum IGF-1 had not reached median survival. In the patient group with IGF-1 levels above 13 nM, median survival was 62 months (P =.006). These findings support the hypothesis of a role for IGF-1 in myeloma disease progression.