The excretion of the widely used antiarrhythmic agent procainamide into the bile and saliva of rats with chronic renal failure (CRF) induced by a two stage-total nephrectomy was studied. Chronic renal failure significantly elevates plasma, salivary, and biliary procainamide levels compared to normal and sham operated rats at all time periods studied. However, while the increase in salivary excretion parallels that of plasma, biliary excretion does not. Results indicate that there is probably saturation of an active transport mechanism for procainamide into bile and that bile cannot compensate for increased drug levels which accumulate during CRF. Salivary excretion, though increased during CRF, also cannot compensate for elevated procainamide levels. Moreover, CRF does not appear to impair non-microsomal acetylation of procainamide, the major biotransformation reaction in the metabolism of this drug.