Sodium fluoride increased the force of contraction in isolated guinea-pig papillary muscles concentration dependently, starting at 3 mmol/1. Sodium fluoride inhibited phosphorylase phosphatase activity in homogenates from guinea pig hearts, starting at 1 mmol/1. The positive inotropic effect of 3 mmol/1 sodium fluoride was not accompanied by an increase in cAMP content in guinea-pig papillary muscles. In papillary muscles, carbachol or (-)-N(6)-phenylisopropyladenosine reduced the positive inotropic effect of isoprenaline (10 nmol/1) or the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (60 mu mol/1). These negative inotropic effects of carbachol and (-)-N(6)-phenylisopropyladenosine were attenuated by additional sodium fluoride (3 mmol/l). It is concluded that sodium fluoride can impair the signal transduction of muscarinic M2 (carbachol) and adenosine receptor (-)-N(6)-phenylisopropyladenosine) agonists. This effect of sodium fluoride could support the hypothesis that the cardiac effects of muscarinic M2 and adenosine receptor agonists involve, at least in part, the activation of phosphatases.