Insulin has been shown to regulate insulin-like growth factor-binding protein-1 (IGFBP-1) in vivo and in vitro. Insulin resistance is a feature of the polycystic ovary syndrome (PCOS). We have studied the relationship between insulin sensitivity (S1) and the circulating concentration of IGFBP-1 in a group of young women and in some who had PCOS. A case-control study has been carried out comparing reproductively normal women with women with PCOS (defined as women with oligo- or amenorrhea associated with androgen excess). Fifteen women with clinical PCOS and ten age- and weight-matched controls were studied. S1 was measured by the frequently sampled intravenous glucose tolerance test (FSIGT) using the minimal model technique. IGFBP-1, insulin-like growth factor-I (IGF-I) and growth hormone levels were measured before and during the FSIGT. Circulating testosterone, dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) levels were measured while the subjects were fasting. S1 and IGFBP-1 levels were significantly lower in the PCOS group than in controls (S1/10(-5) min-1/pM] mean +/- SE 3.8 +/- 0.8 vs. 8.5 +/- 1.3, p < 0.03; IGFBP-1 [ng/ml] mean +/- SE 26.6 +/- 4.2 vs. 56.0 +/- 5.9, p < 0.005). In women with PCOS, IGFBP-1 concentrations related negatively to the body mass index (BMI) (r = -0.77, p < 0.003) and positively to S1 (r = 0.76, p < 0.003). S1 remained a significant predictor of IGFBP-1 concentrations when controlled for BMI (combined r2 = 0.35, p < 0.05). No relationship was found between androgen levels and IGFBP-1. Insulin sensitivity contributed to the difference in IGFBP-1 levels found in women with PCOS. Whether the reduced concentrations of IGFBP-1 play a role in the pathophysiology of PCOS is uncertain, but it may act to alter delivery of IGF to peripheral tissues in insulin-resistant individuals.