The effects of aminophylline on diaphragmatic muscle contractility were studied in 8 dogs. The relationships of the electromyographic signal from the diaphragm and the pressures developed by this muscle were compared before and after the administration of aminophylline in doses of 6, 20, 40, 80, and 120 mg/kg. Measurements were made during occluded inspiratory efforts at functional residual capacity. In a second group of 4 dogs the relationships were compared while the rib cage expansion was limited by a plaster cast. Finally, in a third group of 4 dogs after the diaphragm had been paralyzed by phrenicotomy, the relationship of pleural pressure to the electromyographic signal of the intercostal muscles was assessed before and after administration of aminophylline. In all cases, aminophylline progressively shifted the electromyographic pressure relationship up and to the left. This effect became significant (p less than 0.01) at a dose of 20 mg/kg, reached a peak at 80 mg/kg, and then declined at a dose of 120 mg/kg. The amount producing blood concentrations closest to the human therapeutic blood concentration was 20 mg/kg. The peak increase in pressure compared with the control values were 58% in the first group, 27% in the second group, and 52% in the third group (p less than 0.01). We conclude that aminophylline increases respiratory muscle contractility in a dose-related manner. This may have important therapeutic and pathophysiologic implications.