We previously predicted that highly lipid soluble antibiotics would be very effective in the treatment of infected cysts in autosomal dominant polycystic kidney disease (ADPKD). This study examines the use of chloramphenicol, a lipid soluble antibiotic with a therapeutic spectrum covering most gram negative organisms, in the treatment of patients with infected polycystic cysts who had not responded to initial antibiotic therapy. Intravenous chloramphenicol was used in five hospitalized patients with serious infections of the renal cysts. Three of the five patients had positive blood cultures. E. coli was grown in all five patients, in three from blood, in two from urine, and four of five patients were initially treated with antibiotics to which the organism was sensitive. Despite favorable sensitivities, none of the reported patients showed clinical response to initial antibiotic therapy. Chloramphenicol treatment was subsequently effective in all cases. One patient ultimately developed an infection with a chloramphenicol resistant organism. We conclude that chloramphenicol is effective in the treatment of infected cysts in ADPKD but that care must be taken in the use of this agent as selection of resistant organisms may occur in patients with recurrent cyst infections.