Maximal relaxation rate (MRR, % pressure fall/10 msec) of the inspiratory muscles is reduced with fatigue. We have investigated whether MRR of esophageal pressure (Pes) generated by voluntary sniffs is decreased by fatigue, and whether sniff nasopharyngeal (Pnp) and mouth (Pmo) MRR reflect these changes. In 10 normal subjects, control MRR of sniff Pes correlated closely to Pnp MRR (r = 0.977, p less than 0.001) and Pmo MRR (r = 0.947, p less than 0.001). To produce inspiratory muscle fatigue, four highly motivated subjects breathed to exhaustion (3 to 6 min) through a high inspiratory resistance. MRR was determined from 10 sniffs for Pes, Pnp, and Pmo before fatigue, and at intervals up to 10 min after fatigue. The subjects showed a mean decrease in sniff Pes MRR of 33% (range, 20 to 42) immediately after fatigue, which returned exponentially to control values within 3 to 4 min. The mean changes in Pes MRR were reflected by similar changes in Pnp MRR, 32% (range, 18 to 43) and Pmo MRR, 33% (range, 21 to 42). Studies were repeated in the four subjects with closely similar results. We conclude that fatigue of the inspiratory muscles reduces MRR of sniff Pes, and that this is reflected in Pnp and Pmo. Sniff Pes, Pnp, and Pmo MRR measurements may provide a useful method for detecting and monitoring fatigue; Pnp and Pmo have the advantage of being less invasive.