1. NiCl2 (cumulative concentrations of 0.56-1.91 mmol 1(-1)) produced concentration-dependent depression of tension developed (Td) and the maximum rate of rise of tension (dT/dt max) of isometric contraction of the isolated rat hemidiaphragm, during direct subtetanic (DST) electrical stimulation, only. EC50 values for NiCl2-induced depression of Td and Dt/dt max were 0.88 +/- 0.06 and 0.83 +/- 0.13 mmol 1(-1), respectively. NiCl2 did not significantly change either parameter of the isometric contraction during direct single-pulse (DSP) electrical stimulation. 2. Maximal depression of Td and dT/dt max, produced by a single concentration of NiCl2 (1 mmol 1(-1)) during DST electrical stimulation was obtained 20 min after addition of the drug in the bathing medium. 3. In the normal Tyrode solution, addition of CaCl2 (final concentration of 5.86 mmol 1(-1)) almost completely antagonized the depressant effect of NiCl2 (1 mmol 1(-1)) on Td and dT/dt max during DST electrical stimulation. In the calcium-free solution, the depression both of Td and dT/dt max produced by NiCl2 (1 mmol 1(-1)) was significantly more pronounced in comparison with the effect of NiCl2 in the normal Tyrode solution. 4. L-calcium channel activator, Bay K 8644 (25 mumol 1(-1)), significantly potentiated both Td and dT/dt max during DST electrical stimulation, but NiCl2 (1 mmol 1(-1)) decreased both parameters of the isometric contraction even in the presence of this concentration of Bay K 8644. On the other hand Bay K 8644 (25 mumol 1(-1)) did not antagonize NiCl2-induced depression of Td and dT/dt max. 5. Verapamil (2.5 mumol 1(-1); 45 min of incubation) and lidocaine (0.10 mmol 1(-1); 30 min of incubation) significantly potentiated the depression of Td and dT/dt max, produced by NiCl2 (1 mmol 1(-1), during DST electrical stimulation. The addition of CaCl2 (final concentration of 7.20 mmol 1(-1)) in the bathing medium only partially antagonized the depressant synergistic action of both verapamil or lidocaine and NiCl2 on Td and dT/dt max. 6. Forskolin (cumulative concentrations of 2.60-44.20 mumol 1(-1)) fully antagonized NiCl2-induced depression of both Td and dT/dt max; propranolol (1 mumol 1(-1)) did not abolish this antagonizing action of forskolin. Also, NiCl2 (cumulative concentrations of 0.56 -1.54 mmol 1(-1)) did not change potentiating effect of forskolin (23.4 mumol 1(-1)).(ABSTRACT TRUNCATED AT 400 WORDS)