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Erythrocyte adenosine deaminase (ADA) activity was assessed in 33 children born to human immunodeficiency virus (HIV)-positive mothers. The enzyme values were significantly increased in infected, symptom-free children compared with a control group of HIV-negative subjects (mean ± SD: 0.34 ± 0.01 unit/ml red blood cells (RBC) vs. 0.25 ± 0.04 unit/ml RBC, P < 0.01) and a further significant increase was found in symptomatic children (0.45 ± 0.02 unit/ml RBC, P < 0.01 vs. infected, symptom-free children). ADA values were slightly enhanced also in the group of infants in whom the state of HIV infection was indeterminate (0.29 ± 0.03 unit/ml RBC, P not significant vs. controls).These data indicate that increased erythrocyte ADA activity may be a useful though indirect marker of HIV infection in children at risk and be of possible prognostic relevance. Since increased values were present also in children without overt infections or hematologic disorders, and ADA activity of erythrocytes obtained from healthy donors did not increase after 1 hour incubation with patients' serum, HIV could induce large amounts of cellular enzyme infecting directly erythroid precursor cells.