Objective: In aging populations, poor handgrip strength has been associated with physical disability and mortality. IGF1 is an important mediator of muscle growth and regeneration affecting muscle function. We studied the relationship between circulating levels of IGF1, its binding protein 3 (IGFBP3), and handgrip strength and physical performance in middle-aged- and oldest-old subjects. Design: Cross-sectional analysis in two different cohorts composed of middle-aged- (n=672, mean 63.9±6.7 years) and oldest-old subjects (n=272, all 89 years). Methods: Handgrip strength, functional performance and ability, and serum levels of IGF1 and IGFBP3 were measured in all subjects and analyzed by linear regression for men and women separately. Results: IGF1 and IGFBP3 levels declined with chronological age and were positively associated with handgrip strength in middle-aged- and oldest-old women (both, P<0.05), but not in men of either age group. Furthermore, higher serum levels of IGF1 were associated with slower walking speed in oldest-old men (P=0.012), and serum levels of IGFBP3 were positively associated with activities of daily living in the oldest-old women (P=0.002). Conclusion: The significant relationship between IGF1 levels and muscle strength found in women but not in men suggests a gender-specific influence of IGF1 on muscle strength. Further studies are necessary to test the relationship with physical performance.