Peritoneal sclerosis is one of the most important complications of peritoneal dialysis (PD) treatment. Encapsulating peritoneal sclerosis (EPS) represents the most advanced stage of that disease and has a high mortality. No therapy of choice has been established for sclerosing peritonitis, although many have been proposed, with variable results. Tamoxifen has been successfully used in the treatment of patients with fibrosing diseases, mainly retroperitoneal fibrosis. Our purpose in the present study was to investigate whether treatment with tamoxifen in PD patients with peritoneal sclerosis has a beneficial effect. Among more than 450 patients treated in our program since 1980, 23 were diagnosed with peritoneal sclerosis. Of those 23.9 were treated with tamoxifen [20 mg every 12 hours: tamoxifen group (TG)] for a mean period of 14.5 +/- 7 months (range: 6-30 months). The other 14 patients received no treatment and were considered the control group (CG). Both groups were similar in demography and peritoneal antecedents. Follow-up was longer in CG than in TG (mean: 47 months vs. 29 months), but the difference did not reach statistical significance. Mild thrombopenia in 1 patient was the only toxic effect observed with the use of tamoxifen. In CG, 4 patients developed EPS and died--3 of them during the first 6 months after diagnosis. No patient treated with tamoxifen developed EPS. Overall mortality was significantly higher in CG (71% vs. 22%, p = 0.03). Although follow-up was longer in CG, half the patients in that group died during the first 2 years after diagnosis. Our experience suggests that treatment with tamoxifen of patients diagnosed with peritoneal sclerosis diminishes the related complications and significantly reduces mortality, at least in the short- to mid-term. However, a prospective therapeutic trial is required to confirm our results.