The effects of total ischaemia, subtotal ischaemia, respiratory and metabolic acidosis on the mechanical function and tissue pH (pH_t) of the isolated interventricular septum of the rabbit heart were studied. pH_t was stable in perfused tissue, and responded rapidly and completely to changes in perfusate pH. A fall in pH_t was apparent within 5 s of the onset of total ischaemia. pH_t fell continuously during ischaemia, the fall after 60 min being 1.41 ± 0.09 units. Developed tension fell to 9 ± 1% of control after 15 min, but the onset of acidosis preceded any decline in mechanical function. pH_t and developed tension returned rapidly towards control on reperfusion. In subtotal ischaemia pH_t fell more slowly and the overall change was smaller than in total ischaemia. Comparison of the relationships between developed tension and pH_t in ischaemia and respiratory acidosis suggests that the fall of pH in ischaemia is sufficiently large and rapid in onset to account for most of the early decline in tension. The existence of other concurrent mechanisms has not been excluded.