The membrane electrical properties and resting ionic conductances of frog semitendinosus muscle fibres were studied in vitro at 25 degrees C with the two-micro-electrode cable technique, in the presence of an activator or inhibitor of protein kinase C (PKC) or in the presence of an activator of adenylate cyclase. The PKC activator, 4 beta-phorbol 12,13-dibutyrate (4 beta-PDB), reduced chloride conductance (GCl) at concentrations greater than 1 microM and did not affect potassium conductance (GK). At 150 microM, the maximum concentration of 4 beta-PDB tested, GCl was reduced by 42%. The "inactive" phorbol ester 4 alpha-phorbol 12,13-dibutyrate did not affect GCl or GK. The inhibitory effect of 4 beta-PDB on GCl was prevented by pretreatment of the muscle preparation with the PKC inhibitor staurosporine. The adenylate cyclase activator forskolin (1.5-8 microM) significantly increased the GK of the fibres, without affecting GCl. Thus, we conclude that frog skeletal muscle GCl, unlike rat muscle GCl, is relatively insensitive to activators of PKC. Moreover, in frog muscle, protein kinase A is a likely modulator of GK, but not GCl.