SummarySerum putrescine (Pu), spermidine (Sd), spermine (Sp), and plasma diamine oxidase activity (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 ± 0.07nmoles/ml), and Sp (0.33 ± 0.08 nmoles/ml) were higher (P< 0.001) in 17 control childrenversus16 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)versus61 healthy adults (5.7 ± 0.07). Levels ≥ +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 ≥ +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.