Insulin-like growth factors (IGFs) are potent mitogens that stimulate the growth of prostate cells. In serum, IGFs circulate bound to IGF-binding proteins (IGFBPs), which modulate their proliferative action. We studied the electrophoretic pattern of IGFBPs in the serum of patients with prostate cancer and in individuals with increased serum levels of prostate-specific antigen (PSA) in the absence of prostate malignancy. Serum IGFBP-2 was dramatically increased in patients with metastatic prostate cancer compared with healthy controls (23.83 +/- 6.93% vs. 2.95 +/- 0.52% of total serum IGFBPs; P < 0.02). A moderate rise in IGFBP-2 was also observed among patients with increased PSA without malignancy. In contrast, a decrease in serum IGFBP-3 was detected in most patients with metastatic prostate cancer (68.2 +/- 9.1% vs. 95.4 +/- 0.9% of total serum IGFBPs; P < 0.02) and was more pronounced in advanced cases. A highly significant correlation between serum IGFBP-2 and PSA levels was found (r = 0.62; P < 0.002), with a significant negative correlation between serum PSA and IGFBP-3 (r = -0.63; P < 0.002). We suggest that IGFBPs may be involved in growth modulation of prostate malignancy and that alterations in their serum levels may serve as a marker for prostate cancer.