Salivary immunoreactive insulin was measured in 45 insulin-treated diabetic patients directly from saliva samples by a radioimmunoassay procedure. Mean and median fasting salivary immunoreactive insulin was respectively 88.5 and 54.0 pmol/L (range 12.2-633.6 pmol/L); fasting salivary insulin values were positively correlated with steady-state plasma free-insulin levels measured in immediately extracted plasma samples (r = 0.62, p less than 0.001) and with daily insulin dose (r = 0.32, p less than 0.05). After subcutaneous injection of 15 U regular insulin in 6 type 1 diabetic patients, salivary insulin concentrations increase reflected that of plasma free-insulin during a 6 h period although with a 60 min time lag. Mean salivary insulin values and plasma free-insulin concentrations were significantly correlated to each other both at each time point (p less than 0.001) and when the mean salivary insulin levels were plotted against the mean plasma free-insulin values 60 min earlier (p less than 0.001). These results suggest that the measurement of salivary immunoreactive insulin (that is easier, faster and cheaper than plasma free-insulin assay) may be usefully employed as an approximation of plasma free-insulin concentrations for clinical and research purposes in patients with circulating anti-insulin antibodies.