The pharmacokinetics of piperacillin given intravenously (1 or 2 g) to nine patients with chronic renal failure and undergoing continuous ambulatory peritoneal dialysis was intermediate between values obtained in healthy volunteers and in patients with renal insufficiency studied between dialyses: half-life, 2.4 h; total clearance, 100 mL/min; urinary or peritoneal clearance, 3 mL/min. The intraperitoneal administration of piperacillin in dialysis fluid (400 mg or 1 g to five patients) increased the half-life (6 to 7 h) and decreased the volume of distribution of about two thirds. In both instances, the area under the curve was well correlated with dosage. The absorption of piperacillin by an inflamed peritoneum in eight patients suffering from peritonitis and treated with 400 mg, 1 g, or 2 g, was increased and returned to normal concurrently with care. Consequently, the recommended dosage is intravenous administration of 2 g of piperacillin every 8 h or intraperitoneal administration of 1 g every 6 h in the dialysate. With such conditions, serum concentrations greater than minimal inhibitory concentrations and sufficient to avoid dissemination of piperacillin-susceptible organisms without risk of accumulation are obtained.