Effective prophylaxis exists against Pneumocystis carinii pneumonia, a major cause of illness and death among human immunodeficiency virus-infected children and adults. While adults with CD4 counts less than 0.2 x 10(9)/L are at highest risk for Pneumocystis carinii, clinical or laboratory markers of high risk in children infected with the human immunodeficiency virus have not yet been established. A chart review of 13 infants with perinatally acquired human immunodeficiency virus infection and children with Pneumocystis carinii pneumonia revealed that infants younger than 12 months developed Pneumocystis carinii pneumonia despite CD4 counts that were normal by adult standards. In contrast to the markedly increased serum IgG levels seen in most children infected with the human immunodeficiency virus, five children with Pneumocystis carinii pneumonia had IgG levels less than 3.0 g/L. Twelve patients had pre-existing symptoms consistent with human immunodeficiency virus infection before the episode of Pneumocystis carinii pneumonia. In addition to clinical symptoms, low IgG levels and CD4 counts adjusted for age may serve to identify those children who are most at risk for Pneumocystis carinii pneumonia and therefore candidates for prophylaxis. Prophylaxis should be offered to all infants under age 12 months with proven, or clinical symptoms compatible with, human immunodeficiency virus infection. For children older than 12 months, CD4 counts less than 0.3 x 10(9)/L appear to be predictive of risk for Pneumocystis carinii pneumonia, and these children should also receive prophylaxis.