Maintaining patients with end-stage renal disease (ESRD) on renal replacement therapy is expensive and it is important to increase efforts towards reducing the incidence of ESRD. For this, a sound knowledge of the magnitude of the problem is necessary. This study was undertaken to estimate the incidence of ESRD in two regions of Saudi Arabia namely: Gizan, situated in the Southern area with a population of 654,685; and Al-Madinah, situated in the North Western area with a population of 828,477. All general hospitals and primary care centers under the Ministry of Health in the two regions were included in the study. Those patients in whom two consecutive serum creatinine values above 265 micromol/L were recorded were recruited into the study. There were no non governmental centers offering care for patients with renal failure in the study regions at the time of the study. A total of 108 patients in Al-Madinah region and 187 patients in Gizan fulfilled the criteria of the study. Sex distribution was similar in both regions, 61% male and 39% female. There were 71.3% Saudi and 28.7% Non-Saudi patients in Al-Madinah and 65.2% Saudis and 34.7% Non-Saudi patients in Gizan. Analysis of age distribution showed that the highest prevalence occurred among patients between 41 and 60 years of age in Al-Madinah whereas in Gizan it was between 21 to 50 years. The annual incidence of ESRD in Al-Madinah was 65.2 per million population (PMP) and in Gizan 189 PMP. The higher incidence in Gizan may be due to ethnic, socio-economic and environmental factors. A large scale study covering all parts of the Kingdom is needed to throw more light on such variations in the incidence of ESRD in the Kingdom.