Apalcillin is a new semisynthetic penicillin used as a sodium salt. More than 4,000 patients have been treated with this antibiotic, but increased serum creatinine levels were noted in 18 cases. In 5 of these cases, apalcillin was possibly responsible, and in 13 it was doubtful. We decided to study renal function of normal volunteers treated with 4 g of apalcillin. Three periods were studied: a pretreatment control period of 80 min followed by a treatment period of 60 min and a posttreatment period of 40 min. Inulin and p-aminohippurate (PAH) infusion were continued during all three periods. At the beginning of the treatment period, 2 g of apalcillin was injected as a bolus, followed by infusion of 2 g of apalcillin over 1 h. Urinary volume was measured every 20 min. Creatinine, insulin, and PAH clearances and urinary excretion of sodium, potassium, calcium, and magnesium were calculated for each period. Urinary beta-2-microglobulin excretion was also assessed. Analysis of variance was done. We observed no variation in clearances of creatinine or inulin or in urinary electrolyte output. PAH clearance was significantly decreased during apalcillin infusion. Apalcillin appeared to compete with PAH for proximal tubular secretion but induced no further renal dysfunction.