STUDY DESIGN Retrospective cohort. OBJECTIVES To investigate the effects of lifetime exposure to commonly suspected risk factors on disc degeneration using magnetic resonance imaging, and to estimate the effects of these suspected risk factors relative to age and familial aggregation, reflecting genetic and shared environmental influences. SUMMARY OF BACKGROUND DATA Structural and biochemical changes associated with disc degeneration are suspected as the underlying conditions of many back-related symptoms. Little is known about the determinants of disc degeneration. METHODS Based on lifetime discordance in suspected environmental risk factors for disc degeneration, 115 male identical twin pairs were selected. An in-depth interview was conducted of occupational and leisure time physical loading, driving, and smoking. Disc degeneration was evaluated using observational and digital magnetic resonance imaging assessment methods. RESULTS Heavier lifetime occupational and leisure physical loading was associated with greater disc degeneration in the upper lumbar levels (P = 0.055 - 0.001), whereas sedentary work was associated with lesser degeneration (P = 0.006). These univariate associations did not reach statistical significance in the lower lumbar region. In multivariate analyses of the upper lumbar levels, the mean job code explained 7% of the variability in observational disc degeneration scores; the addition of age explained 16%, and familial aggregation improved the model such that 77% of the variability was explained. In the lower lumbar levels, leisure time physical loading entered the multivariate model, explaining 2% of the variability. Adding age explained 9%, and familial aggregation raised the variability in disc degeneration scores explained to 43%. CONCLUSIONS The present study findings suggest that disc degeneration may be explained primarily by genetic influences and by unidentified factors, which may include complex, unpredictable interactions. The particular environmental factors studied, which have been among those most widely suspected of accelerating disc degeneration, had very modest effects.