The renal proximal tubule (PT) is a major site for maintaining whole-body pH homeostasis and is responsible for reabsorbing ~80% of filtered bicarbonate (HCO₃^-), the major plasma buffer, into the blood. The PT adapts its rate of HCO₃^- reabsorption (JHCO₃) in response to acute acid-base disturbances. Our laboratory previously showed that single isolated perfused PTs adapt JHCO3 in response to isolated changes in basolateral (i.e., blood-side) [CO₂] and [HCO₃^-], but surprisingly not pH. The response to [CO₂] is blocked by the ErbB-family tyrosine kinase inhibitor PD168393. In the present study, we expose enriched rabbit PT suspensions to five acute acid-base disturbances for 5 and 20 min, using a panel of phosphotyrosine (pY)-specific antibodies to determine the influence of each disturbance on pan-pY, ErbB1-specific-pY (four sites), and ErbB2-specific-pY (two sites). We find that each acid-base treatment generates a distinct temporal pY pattern. For example, the summated responses of the individual ErbB1/2-pY sites to each disturbance show that metabolic acidosis (normal [CO₂], reduced [HCO₃^-]) produces a transient summated pY decrease (5 vs. 20 min), whereas metabolic alkalosis produces a transient increase. Respiratory acidosis (normal [HCO₃^-], elevated [CO₂]) has little effect on summated pY at 5 min but produces an elevation at 20 min, whereas respiratory alkalosis produces a reduction at 20 min. Our data show that ErbB1 and ErbB2 in the PT respond to acute acid-base disturbances, consistent with the hypothesis that they are part of the signaling cascade.