To investigate the hypothesis that renal secretion of penicillins is enhanced in cystic fibrosis the maximal tubular secretion rate (Tmax) of ticarcillin and the serum concentration of ticarcillin at half-maximal secretion rate (TC50) were determined in patients with cystic fibrosis (n = 6) and control subjects (n = 6). Each subject received three consecutive constant-rate intravenous infusions of ticarcillin (4, 13, and 70 mg/kg/hr; 2 1/2 hours each) simultaneously with a constant-rate (30 mg/kg/hr) infusion of insulin. Urine samples were collected at 1/2-hour intervals and serum samples at the midpoint of the urine collections. Ticarcillin and inulin concentrations in serum and urine were determined by high-performance liquid chromatographic and a spectrophotometric method, respectively. Ticarcillin serum protein binding was determined by ultrafiltration. Steady-state ticarcillin serum concentrations were achieved at all three infusion rates. The TC50 was significantly lower (p < 0.05) in patients with cystic fibrosis (33.7 +/- 12.2 micrograms/ml) compared with that in control subjects (77.6 +/- 38.4 micrograms/ml). In contrast, the Tmax was similar (cystic fibrosis, 0.25 +/- 0.12 mg/min/kg; control, 0.22 +/- 0.14 mg/min/kg; p > 0.05). These data indicate that renal clearance of penicillins is enhanced in cystic fibrosis because of greater affinity of the renal secretory system for these drugs.