Serum putrescine (Pu), spermidine (Sd), spermine (Sp), and plasma diamine oxidase ativity (DAO) were determined in cystic fibrosis (CF) homozygotes and heterozygotes plus age-matched controls. Mean (+/- S.E.) levels of Pu (0.51 +/- 0.06 nmoles/ml), Sd (0.63 +/- 0.07 nmoles/ml), and Sp (0.33 +/- 0.08 nmoles/ml) were higher (P < 0.001) in 17 control children versus 16 healthy adults (Pu = 0.15 +/- 0.04; Sd = 0.14 +/- 0.03; Sp = 0 in all). All 4 CF adults tested, but only 3 of 24 CF children, had increased polyamines relative to age-matched controls. Pu (0.33 +/- 0.04), Sd (0.33 +/- 0.05) and Sp (0.16 +/- 0.12) were increased (P < 0.001) in 11 adult heterozygotes; in turn, Pu (0.56 +/- 0.11; P < 0.025) and Sd (0.86 +/- 0.22; P < 0.005) were higher in the adult CF patients than in the heterozygotes. Plasma DAO was higher (P < 0.001) in 45 control children (9.3 +/- 0.7 units/ml) versus 61 healthy adults (5.7 +/- 0.07). Levels greater than or equal to +2 S.D. for controls occurred in 8 (21%) of 39 CF patients. Plasma DAO (19 +/- 4.8) was increased (P < 0.001) in 27 adult heterozygotes; 10 (37%) had values greater than or equal to +2 S.D. for normal adults. One or more polyamines and/or DAO were increased in each of 11 heterozygotes in whom all parameters were measured. These composite abnormalities might be considered as a potential means for identification of asymptomatic CF heterozygotes.