The presence of hypertrophic mesothelial cells (HMCs) in peritoneal effluent (PE) has been considered a possible marker for peritoneal sclerosis. We conducted the present study to evaluate if the presence of HMCs in PE or in culture was related to peritoneal function alterations or to the development of sclerosing peritonitis. We prospectively studied 32 new peritoneal dialysis (PD)patients every 4 months, determining the presence of HMCs in culture (completing 129 studies in total). We isolated mesothelial cells from nocturnal PE and cultured them ex vivo in T-25 flasks. Cell morphology was estimated using the May-Grünwald/Giemsa method. We also examined the histories of a large patient group to determine HMCs directly in PE, and we evaluated 4 of those patients (6%) who showed persistent HMCs. In 10 of 32 prospectively studied patients, we found HMCs during the culture phase. The cells appeared in the first evaluation in 4 patients and in subsequent cultures in the remaining 6 patients. Ultrafiltration (UF) and solute transport capacity in the 10 patients were similar to those of patients who did not show HMCs. Demographic parameters were not different between the two groups. None of the prospectively studied patients showed any clinical or peritoneal functional abnormality during the study. Cultures performed after the observation of HMCs showed very poor growth capacity. The evolution of the 4 patients in the historic group occurred as follows: We 1 patient transferred to hemodialysis 2 years after the observation of HMCs. 1 patient died of an unrelated cause after 1 year on PD. 1 patient received a successful kidney graft 5 years after the observation of HMCs. 1 patient developed type I UF failure 10 years after the first observation.