The effects of the cardioplegic solution HTK on membrane potential (EM) and intracellular K and Na activities (a~, a~a) were studied in sheep cardiac Purkinje fibres by means of conventional and ion-selective microelectrodes. HTK contains (raM): Na 15, K 10, Ca 0, Mg 4, histidine 180. (1) In control conditions EM was --74.3_+3.3 mV (n=25), ak was 116.4_+4.1 mM (n=7) and a~a was 8.2_+ 1.4mM (n= 15). ( 2) Exposure to HTK led to a depolarization to -59.7 _+ 3.6 mV (n --= 25) which exceeded by about 5-7 mV that induced in a Tyrode solution of 10 mM K and in a modified HTK solulion supplemented by 2 mM Ca (n = 6). (3) Addition of 0.5 mM barium eliminated the difference in the steady-state depolarization. ( 4) HTK superfusion increased ak to 120.1 _+ 4.4. mM (n = 7) and decreased a~a to 3.9 _+ 0.9 mM (n = 15). ( 5) The decrease in aha was insensitive to amiloride (1 raM) and to external alkalization but was slightly increased by addition of 2 mM calcium 9 (6) When the calcium in Tyrode solution was lowered from 2.0 mM to 0.05 mM, a~a hardly decreased during subsequent exposure to unmodified HTK and it increased in the presence of 0.1 mM dihydroouabain. We propose the hypothesis (1) that the difference in membrane depolarization between HTK and a 10 mM K-Tyrode is caused by a decrease in K conductance by the HTK solution and (2) that the a~a decline mainly results from a coupled Ca influx via Na-Ca exchange due to a delayed washout of external calcium.