The frequency of multiple sclerosis (MS) varies greatly in different parts of the world, but also within some countries. Many epidemiological surveys of geographical pattern of MS identified areas of different risk of MS in relation to the latitude. The study of disease clusters is a potentially powerful strategy in revealing the aetiology of a disease. A series of space and time clusters of MS has been described over the years, especially in islands' populations. The Belgrade region is located on 628 m height above the sea level, between latitudes 44 and 45 degrees north of the equator, and longitudes 20 and 21 degrees east of the Greenwich. The district of Belgrade is divided into 16 municipalities and extends over an area of 3,222 km2. According to the 1991 census, the area has a population of 1,602,226 inhabitants. All persons who were affected and/or died from MS with residence in Belgrade region had been registered from January 1,1985 to December 31,1996, on the basis of a retrospective analysis of hospital records. The main sources for this study were hospital case records in all 4 neurological hospitals in Belgrade (Institute of Neurology of the Serbian Clinical Centre, which is the primary referral national centre for suspected/diagnosed MS patients in Serbia, and three Departments of Neurology which belong to Zvezdara Clinical Centre, Dr. Dragisha Mishovitsh Clinical Centre, and Military Medical Academy). Only clearly diagnosed and fully documented cases with clinically and laboratory supported MS according to Poser's criteria were included. For each patient, two neurologists (JD and NS) and one epidemiologist (TP) reviewed all data collected in order to verify the validity of the diagnosis. The prevalence, as a number of persons with MS in the population at risk, was calculated on December 31, 1996, for each municipality and for the Belgrade population as a whole. The Belgrade municipalities were categorized according to MS prevalence level, as category 1 (> or = 50/100,000)--Stari Grad, Vrachar, Vozhdovac, Rakovica, Barajevo, Zvezdara; category 2 (30-49/100,000)--Savski Venac, Novi Beograd, Chukarica, Zemun; and category 3 (< 30/100,000)--Palilula, Sopot, Grocka, Obrenovac, Lazarevac and Mladenovac. The geographic distribution was estimated according to the prevalence of MS, and hypothetical cluster of the disease was tested by chi-square test. On December 31, 1996, the prevalence of MS in the Belgrade population was 44.87/100,000. The highest MS prevalence was registered in the municipality of Vrachar (74.63/100,000), and the lowest in the municipality of Mladenovac (17.73/100,000) (Table 1). Municipalities which are grouped within the 3 categories are not statistically significantly clustered (chi-square = 1.479, p > 0.05).