Simultaneous measurements of mouth pressure at the end of the first 0.1 s of inspiratory occlusion (P0.1) at functional residual capacity and the maximum rate of rise of this pressure (dP/dt max) were made repeatedly in 5 normal subjects during resting respiration; the coefficient of variation of dP/dt max was 36.2%, compared with 50.6% for P0.1. During both isocapnic hypoxia and hyperoxic hypercapnia in 5 normal subjects, there was a close correlation between ventilation (.ovrhdot.VE) and both P0.1 and dP/dt max, and between end-tidal PCO2 or PO2 and P0.1 and dP/dt max; during both procedures there was a close correlation between P0.1 and dP/dt max. The time at which dP/dt max occurred (Tmax.) was not correlated with changes of dP/dt max in either procedure. Tmax was greater than 0.12 s in most studies. The regression coefficients of P0.1 and dP/dt max on .ovrhdot.VE were significantly different in hypoxia as compared with hypercapnia in 4 out of the 5 subjects; on repeated hypercapnic stimulation in 2 out of 3 subjects these regression coefficients again varied significantly. Changes in lung volume or inspiratory volume-timing relationship were not responsible for these differences. Mouth occlusion pressure, as reflected by P0.1 or dP/dt max, is a complex variable, reflecting the motor output of the respiratory center, but also affected by random variations in the measurements and probably by changes in lung volume.