The mechanical response of the inferior glenohumeral ligament to varying subfailure cyclic strains was studied in 33 fresh frozen human cadaver shoulders. The specimens were tested as bone-ligament-bone preparations representing the 3 regions of the inferior glenohumeral ligament (superior band and anterior and posterior axillary pouches) through use of uniaxial tensile cycles. After mechanical preconditioning, each specimen was subjected to 7 test segments, consisting of a baseline strain level L1 (400 cycles) alternating with either 1 (group A, 10 shoulders), 10 (group B, 13 shoulders), or 100 (group C, 10 shoulders) cycles at increasing levels (L2, L3, L4) of subfailure strain. Cycling to higher levels of subfailure strain (L2, L3, L4) produced dramatic declines in the peak load response of the inferior glenohumeral ligament for all specimens. The group of ligaments subjected to 100 cycles of higher subfailure strains demonstrated a significantly greater decrease in load response than the other 2 groups. Ligament elongation occurred with cyclic testing at subfailure strains for all 3 groups, averaging 4.6% +/- 2.0% for group A, 6.5% +/- 2.6% for group B, and 7.1% +/- 3.2% for group C. Recovery of length after an additional time of nearly 1 hour was minimal. The results from this study demonstrate that repetitive loading of the inferior glenohumeral ligament induces laxity in the ligament, as manifested in the peak load response and measured elongations. The mechanical response of the ligament is affected by both the magnitude of the cyclic strain and the frequency of loading at the higher strain levels. The residual length increase was observed in all of the specimens and appeared to be largely unrecoverable. This length increase may result from accumulated microdamage within the ligament substance, caused by the repetitively applied subfailure strains. The clinical relevance of the study is that this mechanism may contribute to the development of acquired glenohumeral instability, which is commonly seen in the shoulders of young athletes who participate in repetitive overhead sports activities.