We determined the concentrations of clindamycin and gentamicin in fluid aspirated from 16 cysts of a surgically excised polycystic kidney. The patient had received both drugs intravenously for seven days before nephrectomy. The cysts were grouped into proximal (pH greater than 6.5) and distal (pH less than 6.5) types according to the pH of the fluid. In nine proximal cysts the mean concentration of gentamicin was 1.3 +/- 0.2 and that of clindamycin was 9.2 +/- 2.3 micrograms/mL. In seven distal cysts the gentamicin concentration was 0.7 +/- 0.2 micrograms/mL and the clindamycin concentration was 34.0 +/- 5.2 micrograms/mL. Plasma gentamicin was 3.8 (peak) and 1.9 (trough) micrograms/mL, and clindamycin was 3.9 micrograms/mL (random). Clindamycin cyst concentrations showed an inverse correlation with cyst fluid pH (r2 = 0.78). These studies confirm that in autosomal dominant polycystic kidney disease (ADPKD), certain cysts develop steep pH gradients between fluid and plasma and indicate that intracystic pH determines the extent to which basic lipophilic antibiotics accumulate in the fluid. Lipid-soluble antibiotics with relatively alkaline pKaS may be useful in the treatment of infected renal cysts.