OBJECTIVE: We sought to measure the mechanical baseline behavior of fetal membranes in order to determine constitutive mechanical model parameters for fetal membranes, and to examine their relation to molecular correlates for mechanical function, i.e. collagen and elastin. STUDY DESIGN: The uniaxial stress-strain response of nine human term fetal membranes was measured. Methods of nonlinear continuum mechanics were applied for the analysis of the stress-strain curves. Thickness of amnion and chorion were determined from histologic sections for each fetal membrane sample. Complementary biochemical analysis was performed to quantify the soluble collagen and soluble elastin components for each sample. RESULTS: We report a straightforward histologic modality for measurements of amnion and chorion thickness. Average thickness of the amnion and chorion layers were 111+/-78 microm, and 431+/-113 microm, respectively, which are about twice larger than previously reported. The average content of acid-soluble elastin was 2.1% of wet weight and the one of pepsin/acetic acid-soluble collagen was 10.5% of dry weight. Our data show an inverse proportionality between soluble elastin and soluble collagen content. The low strain elastic modulus ranged between 10 and 25 kPa. Correlations were found between biochemical data and mechanical parameters: there is clearly a direct proportionality between small strain elastic modulus and elastin content. Further, a (less pronounced) direct correlation was observed also between soluble collagen content and the parameter governing the increase in stiffness at larger strains in the nonlinear mechanical model. The mechanical tests revealed a relatively low variability for samples from the same membrane but a large variation between donors. The proposed nonlinear model provides a good fit of the experimental data, with a coefficient of determination, R(2), typically in the range of 0.94. Membranes failure originated at the clamping points thus impairing the quantification of ultimate stress and strain. Thus, no correlation was found between maximum stress and collagen or elastin content. CONCLUSIONS: This study provides a starting point for comprehensive quantitative analysis of the relationship between fetal membranes microstructure and their nonlinear deformation behavior. These insights could become useful in identifying potential medical interventions to prevent membranes rupture.