With the use of quantitative genetic models, the relative importance of genetic and environmental influences on serum levels of insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), and insulin was evaluated in 248 pairs of middle-aged and elderly Swedish twins reared apart and reared together. Heritability estimates (the relative influence of genetic effects) were 48% for insulin, 63% for IGF-I, and 36% for IGFBP-1. There was no indication of differences in heritability estimates for IGF-I, IGFBP-1, and insulin across age and gender groups. Nonshared environmental influences, unique to individuals, explained the remaining variance in the measures. The genetic influences on IGF-I levels were independent of the genetic influences on insulin and IGFBP-1 levels. However, a small, but significant, proportion of the genetic variation in IGFBP-1 was in common with genetic influences for insulin. Furthermore, genetic effects explained 36% of the phenotypic correlation between IGFBP-1 and insulin, whereas the phenotypic associations between IGF-I and both IGFBP-1 and insulin were entirely attributable to environmental effects. Finally, the phenotypic association between IGF-I and IGFBP-1 was mediated wholly by environmental influences in common with insulin.