Theophylline clearance was estimated by a single-sample technique in 19 subjects with acute clinical respiratory infections. Mean (+/- SD) theophylline clearance during acute illness was 0.044 +/- 0.011 L X h-1 X kg-1 compared to 0.043 +/- 0.012 L X h-1 X kg-1 1 month later. In a subset of five subjects, single-sample clearance estimates were not different from standard multi-sample clearance estimates. Mild upper respiratory infection does not appear to alter theophylline clearance in adults.