We examined neuropathy, ankle pressure index (API), and other factors as predictors of transcutaneous oxygen (TcPO2) in the lower limbs of 657 diabetic subjects. Eligible subjects underwent a clinical assessment that included three standard measures of autonomic neuropathy. TcPO2 measurements were performed at 37 degrees C and 44 degrees C at four lower limb locations. Associations between potential predictors and TcPO2 were tested using univariate and multivariate statistics. Mean TcPO2 at any site did not differ by presence of autonomic neuropathy at either temperature, except for a significantly lower value at 44 degrees C below the knee (56.5 versus 59.2 mmHg, p = 0.021). In multivariate analysis, autonomic neuropathy was significantly and independently related to leg 44 degrees C TcPO2 only (coefficient = -2.6734, p = 0.0182). Much stronger associations were seen between TcPO2 and age, ankle blood pressure, and relative body weight on the plantar foot; and between API, glycosylated haemoglobin, ankle blood pressure, and pedal oedema on the dorsal foot and leg. We conclude that factors related to lower limb TcPO2 vary depending on measurement site. Autonomic neuropathy is not an important determinant of TcPO2 in the feet of diabetic subjects. Although several predictors of TcPO2 were identified, most of the variance of this measurement remains unexplained.