We report the occurrence of multiple leiomyomata and leiomyosarcomata in three children with the acquired immunodeficiency syndrome. The children were infected with human immunodeficiency virus as infants (one perinatally and two through transfusions) and each was profoundly immunosuppressed (absolute CD4 cell count, less than 75/mm3). They experienced multiple infections prior to the diagnosis of neoplasms at ages 4, 5, and 8 years, respectively. The tumors in each case were mainly involving the lungs and gastrointestinal tract. The smooth-muscle origin of the tumors was proved by light and electron microscopy and immunohistochemical staining for muscle-specific actin and desmin. Leiomyomata and leiomyosarcomata are rare tumors in childhood, suggesting a nonrandom association of tumors of smooth-muscle origin and the acquired immunodeficiency syndrome. We postulate that human immunodeficiency virus infection may play a direct or indirect role in tumor formation.