We found cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE) activity to be significantly elevated in the umbilical cord blood mononuclear leukocytes of forty-two children with one atopic parent (3.2 +/- 0.3) and in eighteen children with two atopic parents (4.2 +/- 0.7) as compared to twenty-two children with two nonatopic parents (1.9 +/- 0.2) (p less than 0.005). Among those newborns with one atopic parent, mean PDE activities were significantly elevated in cord blood cells regardless of whether only the father was atopic, thus eliminating the possibility of transplacental enzyme passage. Follow-up evaluations of twenty-four children, age 6 months or older, suggest that infants with elevated PDE activity at birth have an increased likelihood of developing dermatitis and/or "atopic features." Further long-term studies will determine the predictive value of newborn mononuclear leukocyte PDE activity.