The effect of stress deprivation and cyclic tensile loading on the mechanical and histologic properties of the canine flexor digitorum profundus tendon was examined using an in vitro system. Stress deprivation resulted in a progressive and statistically significant decrease in the tensile modulus over an 8-week period. Histologically, stress-deprived tendons demonstrated quantitative changes in the morphology and number of cells and in the alignment of collagen. The change in tensile properties was not associated with an alteration in the water content of the tissue, but the change appeared to be dependent on the presence of a viable cell population. Dead (acellular) tendons did not undergo any alteration in tensile modulus in this in vitro system. In vitro cyclic tensile loading of tendons over a 4-week time period resulted in a significant increase in the tensile modulus (93% of the control) compared with that of the stress-deprived tendons (68% of the control). This loading regimen also maintained the normal histologic pattern of the tendons. The results of this study are similar to those previously reported for in vivo studies and suggest that this in vitro model may represent a valid system with which to test the effects of various stress conditions on the tensile properties of tissues.