Background Overuse tendon injuries are frequent. Corticosteroid injections are commonly used as treatment, although their direct effects on the material properties of the tendon are poorly understood. Purpose To examine the influence of corticosteroids on the tensile strength of isolated collagen fascicles. Study Design Controlled laboratory study. Methods Single strands (300-500 [.mu]m) of rat-tail collagen fascicles were incubated in either high (1 mL of 40 mgmL-1 mixed with 0.5 mL saline 9%) or low (1 mL of 40 mgmL-1 mixed with 2 mL saline 9%) concentration of methylprednisolone acetate (Depomedrol) for 3 or 7 days, while the control segment from the same fascicle was kept in saline (N = 64). After the incubation period, the fascicles underwent displacement to failure in a mechanical test rig at 0.13 mm/s, and thereafter hydroxylysyl pyridinoline and lysyl pyridinoline cross-link content was evaluated in a high-performance liquid chromatography system. Data for each group were analyzed with a 2-way analysis of variance (time × incubation) for ultimate stress (mean ± standard deviation). Results In the high-concentration groups, strength was reduced after 3 (16.6 ± 4.6 MPa) and 7 (8.6 ± 1.7 MPa) days compared to the controls (30.2 ± 5.0 MPa and 25.6 ± 4.6 MPa, respectively; P <. 05). In the low-concentration groups, strength was reduced after 3 (12.0 ± 3.1 MPa) and 7 days (10.9 ± 2.5 MPa) compared to the controls (31.5 ± 5.0 MPa and 32.4 ± 5.6 MPa, respectively; P <. 05). The amount of cross-linking was unaffected by the intervention. Conclusion Data show that the tensile strength of isolated fascicles is markedly reduced after 3-and 7-day incubation in both high and low concentration of corticosteroids, although the observed effect on whole tendon remains unknown. Clinical Relevance Corticosteroids may weaken specific regions of the injected tendon and leave it more prone to rupture. This weakening effect is manifested in the individual collagen fascicles that constitute the tendon.