In a prospective cohort study, the authors examined risk factors for progression of distal symmetric polyneuropathy (DSP) in type 1 (insulin-dependent) diabetes mellitus. The study population consisted of participants in the Sorbinil Retinopathy Trial, a randomized trial of aldose reductase inhibition among patients aged 18-56 years with type 1 diabetes mellitus of 1-15 years' duration. Diagnosis of DSP was based on standardized clinical neurologic evaluation. A total of 407 participants who did not have definite DSP at randomization and had at least one follow-up visit were included in the analysis. Stepwise Cox proportional hazards models were used to examine the independent contribution of baseline variables to progression of DSP. During follow-up (median, 40 months), 68 participants (17%) showed progression to definite DSP. After adjustment for age and treatment assignment, independent predictors of progression to definite DSP were total glycosylated hemoglobin (relative risk (RR) for increase of one percentage point = 1.25; 95% confidence interval (CI) 1.12, 1.39), height (RR associated with being one inch (2.54 cm) taller = 1.15; 95% CI 1.05, 1.26), cigarette smoking (ever vs. never) (RR = 1.87; 95% CI 1.09, 3.21), and female gender (RR = 2.26; 95% CI 1.09, 4.67). These data indicate that, in addition to the previously established role for total glycosylated hemoglobin, other factors including height, cigarette smoking, and female gender may also be independent risk factors for progression of DSP in type 1 diabetes mellitus.