The short wavelength-sensitive (S-) cone electroretinogram (ERG) is selectively reduced in diabetic patients both with and without retinopathy, but the exact mechanism of the vulnerability of the S-cone system is still unclear. This study examined relationships of the S-cone ERG to systemic factors in diabetes. Cone ERGs to different color flash stimuli were examined in the presence of bright white background illumination in 17 diabetic patients without retinopathy and in 17 diabetics with background retinopathy. Relationships of the amplitude and implicit time of the S-cone ERG to the following systemic factors were statistically analyzed: patients' age, hemoglobin A1 level, method of diabetic control, presence of retinopathy, and presence of nephropathy. The amplitude of the S-cone ERG b-wave was significantly reduced in diabetics treated with insulin and in those associated with nephropathy. No significant correlation was found between the S-cone ERG and patient's age, hemoglobin A1 level and presence or absence of retinopathy. A selective reduction of the S-cone ERG is observed in patients whose metabolic control has been poor for a longer period, suggesting that microvascular changes may play a role in the S-cone ERG impairment.