During 1989-90 the Medical Research Programme on AIDS enrolled 4975 children younger than 15 living in a cluster of 15 villages in rural Masaka district, southwest Uganda, into a 3-year prospective study. It examined the data to assess the magnitude of the problem of orphans and the extent to which HIV-1 is contributing to their problems. In this area, it is common for children with both parents alive to live with other relatives (e.g., grandparents) to help with domestic work. 518 (10.4%) children had lost 1 or both parents. These orphans were more likely to have lost a father alone than a mother alone (6.3% vs. 2.8%). 67 (13%) of the 518 orphans (i.e., 1% of all children) had lost both parents. Orphans 0-4 years old and surviving parents of orphans were more likely to be HIV-1 infected than their counterparts (5.6% vs. 0.9% for non-orphans 0-4 years old; p = 0.01 and 15.4% vs. 6.2% for parents of non-orphans; p 0.001). During the follow-up period, 83 parents of previous non-orphans died, leaving 169 orphans. 42.6% of the newly registered orphans had an HIV-1 positive parent. 98 deaths occurred among HIV-1 negative children (7 orphans, 91 non-orphans). No significant difference in mortality rates among HIV-1 negative children existed. Yet, in the 0-4 year old age group, orphans had a higher, but insignificantly so, 3-year mortality rate than non-orphans (22.1 vs. 15.6/1000 person-years). School attendance in the previous 6 months was slightly lower among orphans than non-orphans (75.5% vs. 83.6%) but the difference was insignificant (p = 0.3). Census data indicate that orphanhood has increased by at least 50% in the last 20 years, probably due to the AIDS epidemic. These findings suggest that the community tends to care well for orphans, but if the HIV/AIDS epidemic continues this coping mechanism may be become overly burdened.