We analyzed progressive multifocal leukoencephalopathy (PML) mortality data from 1979 to 1987 and data on persons with acquired immunodeficiency syndrome (AIDS) reported to the Centers for Disease Control (CDC). Based on analyses of multiple-cause-of-death vital statistics, deaths related to PML have increased fourfold from 1.5/10,000,000 persons in 1979 to 6.1/10,000,000 persons in 1987. The increase in the PML annual death rate began in 1984, occurred primarily in men 20 to 49 years of age, and was greatest in states known to have a high incidence of AIDS. In 1987, 56% of death certificates that listed PML as a cause of death also listed human immunodeficiency virus (HIV) infection. Analysis of AIDS case reports to the CDC from 1981 through June 1990 demonstrated that 0.72% of persons with AIDS were reported as having PML. Although most persons with AIDS who had PML were 20 to 49 years of age (84.6%), PML was reported more frequently among persons with AIDS <50 years old than <50 years old. In addition, PML was reported more frequently among persons with AIDS who were exposed to HIV by blood transfusion than those in all other exposure categories. These data demonstrate that the increase in PML mortality from 1979 to 1987 was associated with the large increase in immunosuppressed persons with AIDS.