To examine the responsiveness of the Medical Outcomes Study 36-Item Short Form (SF-36) to the development of diabetes complications over time. We studied a cohort of 331 diabetic veterans participating in a prospective study of risk factors for foot complications. Eight SF-36 scales [general health (GH), physical functioning (PF), social functioning (SF), mental health (MH), physical role (RP), emotional role (RE), bodily pain (BP), and vitality (VT)] and 25 diabetes complications characteristics (DCC) from history and symptom questionnaires and physical exam findings were compared over a mean interval of 3.1 years. The subjects were mostly married, white males with a mean age of 63.5 years, with primarily type 2 diabetes (91%) and a mean diabetes duration of 9.7 years at baseline. There was a statistically significant interval decrease in the GH scale of 6.1 points (effect size [ES] 0.24), PF decreased 9.7 (ES 0.38), SF decreased 5.8 (ES 0.19), PR decreased 14.7 (ES 0.38), BP decreased 4. 0 (ES0.14), VT decreased 4.5 (ES 0.16), total DCC increased by 1.8 (ES 0.53), and hemoglobin A(1c) declined 1.3% (ES 0.48). An increase of >1 DCC was associated with an average loss of 7.2 to 11.8 points on six SF-36 scales (GH, PF, SF, RP, BP, VT). The development of any renal complication was related to decrements in five SF-36 scales (GH, PF, SF, RP, VT) while the appearance of any neuropathy complication was associated with a decline in four SF-36 scales (GH, PF, PR, VT). These results imply that six of the SF-36 scales are responsive to the development of diabetes complications over time among elderly veterans, supporting their use in longitudinal research. Renal and neuropathy complications have the greatest effects on the SF-36.