The clinical significance of respiratory-system load-compensation is unknown. We have measured the responses to random presentation of single, elastic inspiratory loads in 36 subjects: 8 normal personnel (N), 9 with obesity (O), 10 with chronic renal failure under hemodialysis (H), 5 with pneumonia (P), and 4 with interstitial lung disease (CILD). We have expressed these responses as: (1) the ratio of elastance (or rigidity) of the system during loaded breathing to the elastance without loading (E’_RS/E_RS); (2) the ratio of tidal volume (V_τ) achieved when breathing from an inspiratory load to the V_τ predicted in the absence of load compensation (V_TL/V_TP); (3) the ratio of inspiratory flow rates during loaded and unloaded breaths; (4) the ratio of inspiratory time of loaded and unloaded breaths. We found E’_RS/E_RS in the O₂ H and P groups less than that of either CILD patients or N controls (F = 6.79; p < 0.001). Passive elastance (E_Rg) although greater in groups·and H than in N (F = 3.88; p < 0.025) did not account for the difference in E’_RS in all groups. When expressed as V_TL/V_TP, the response to a 37-cm H₂O/1 load for groups H_,·and P was less than that for N (F = 5.51; p < 0.05). Diminished inspiratory time was observed in H_,·and P patients when inspiring from this load. In contrast, inspiratory flow did not differ from that of normal subjects. Nerve conduction velocity was slightly reduced or normal in the H patients. Respiratory load compensation is deficient in H_,·and P patients. The mechanism, which does not involve peripheral neuropathy, is unclear