Objective: Singleton infants with intrauterine growth restriction have an adaptive hormonal profile characterized by decreased levels of IGF-1, IGF-2, IGFBP-3 and insulin and elevated levels of IGFBP-1 and IGFBP-2. This study examined the association between cord serum levels of six growth factors and anthropometric features at birth in twins in order to determine the intrauterine growth factor interactions and to characterize the specific hormonal profile of small discordant twins. Design: Prevalent case-control study. Patients: Twenty pairs of discordant twins (5 monozygotic, 15 dizygotic) and 20 pairs of concordant twins (6 monozygotic, 14 dizygotic) matched for gestational age. Measurements: Cord blood levels of IGF-1, IGF-2, IGFBP-1, IGFBP-3, insulin, leptin and anthropometric measurements at birth. Intra- and inter-pair differences and correlation coefficients were calculated, and the data were fitted to multivariate regression models. Results: In both discordant and concordant groups, the smaller twins had a significantly lower level of IGF-1 (P < 0.03) and significantly higher level of IGFBP-1 (P < 0.02) than their larger cotwins. IGFBP-1 was inversely correlated with IGF-1 (P < 0.05). Insulin levels were significantly higher in the smaller discordant than the smaller concordant twins (P < 0.001) and in the larger discordant than the larger concordant twins (P < 0.004). Among the monozygotic twins, the leptin level was significantly higher in the larger discordant than the larger concordant twins (P < 0.025). Percentage birth weight discordancy was statistically correlated with twin-pair differences in IGF-1 and IGFBP-1. Conclusions: Of the six factors studied, IGF-1 appears to be the main indicator of intrauterine growth. Twin discordancy may involve compensatory rather than adaptive mechanisms or a multihormone relative resistance syndrome.