To determine a reliable quantitative method of measuring diaphragmatic EMG (EMGdi), electrical activity of the diaphragm was obtained via an esophageal electrode during CO2 rebreathing in 6 normal males and processed three different ways: 1) integration (area), 2) as a moving time average, and 3) as a moving time variance. Integrated activity was quantified in terms of total activity and inspiratory activity. In addition, average total activity and average inspiratory activity were calculated. Moving average and moving variance were analyzed in terms of rate of rise (slope) and peak activities. All integration parameters, except average inspiratory activity, were poorly correlated to changes in PCO2, minute ventilation, and inspiratory muscle force, during rebreathing. Moving average and variance responses to rebreathing were linear with high correlation coefficients, with the slope measures showing the overall best correlations. There was no significant difference between average and variance EMGdi parameters in their responses to rebreathing. Time-related quantification of EMGdi, including average inspiratory activity, and particularly moving average and moving variance, appear to be reliable methods for quantitating neural drive to the respiratory muscles during CO2 rebreathing.