Hypoxic chemosensitivity was assessed using 6 methods in 11 patients who had bilateral carotid body resection (termed BR) for asthma 25.1 .+-. 1.2 (SD) yr ago, 10 with unilateral resection (UR) 21.5 .+-. 4.2 yr ago and 5 nonoperated controls (C) approximately matched for age and pulmonary limitation. Six tests were made. Single breath: the difference, .DELTA..ovrhdot.VI in 1/min of the 2nd and 3rd breaths following vital capacity inspirations of 15% CO2 in N2 (test) and 5% CO2 in O2 (control). .DELTA..ovrhdot.VI was 2.2 .+-. 1.4 1/min in BR (P < 0.01), 10.9 .+-. 7.2 1/min in UR and 22.5 .+-. 6.9 1/min in C. Withdrawal during 15 s after 100% O2 terminates hypercapnic hypoxia (PCO2 [Partial pressure of CO2] = control + 5 torr, PO2 [Partial pressure of O2] = 60 torr), the decrement, .DELTA..ovrhdot.VI was 1.3 .+-. 1.2 1/min in BR (P < 0.01), 2.3 .+-. 1.8 1/min in UR (P < 0.01) and 3.6 .+-. 1.4 1/min in C. Progressive hypoxia: isocapnic .DELTA..ovrhdot.VI at PAO2 [alveolar O2 tension] = 40 torr, .DELTA..ovrhdot.V40 = 0.3 .+-. 3.0 1/min in BR (NS [not significant], 6.0 .+-. 4.3 1/min in UR and 17.8 .+-. 8.2 1/min in C. Steady-state CO2 response slope was increased 21% in C by hypoxia (PAO2 = 60 torr), but unaltered by hypoxia in BR and UR subjects. Breath-holding time was shortened by starting at PAO2 = 70 torr (vs. 200 torr, by 7.5 .+-. 4.6 (SE) s in 12 trials in 4 BR patients (P = 0.05). Doxapram, 0.4 mg/kg i.v. increased .ovrhdot.VI at its peak response by 8.0 .+-. 7.5 1/min in 4 BR and by 21.0 .+-. 4.3 in 4 C. Tests 1, 2 and 6 disclose possible peripheral chemosensitivity in some BR patients; no response was detected in tests 3-5. Regenerated carotid sinus nerve endings and aortic bodies are possible sites.