The in vivo effect of aminophylline (theophylline ethylenediamine) on cAMP levels and the mitogenic response of peripheral blood mononuclear cells (PBMC) from preterm infants were investigated. Increased cAMP levels and reduced response of these cells to concanavalin A (Con A) were found in preterm newborns who received intravenous aminophylline. No inhibitory effect of the drug on phytohemagglutinin (PHA)-induced proliferation was observed. cAMP levels of PBMC derived from preterm infants were significantly lower than those of term newborns. The in vitro effect of theophylline on the mitogenic response of PBMC from adults, term and preterm infants was also compared. It was found that PBMC from adults were significantly more sensitive to the inhibitory effect of theophylline on Con A-induced proliferation than were PBMC from either term or preterm infants, whereas the effect of the drug on the mitogenic response to PHA was similar in the three groups. These data suggest differences either in the sensitivity to increased cAMP concentration between PBMC from adults and newborns or in their lymphocyte subpopulations.