Acute bronchiolitis (AB) is a common lung disease in infants manifested clinically by dyspnea and wheezing. The purpose of this study was to measure simultaneous plasma levels of histamine and a stable prostaglandin F2 alpha metabolite [13,14-dihydro-15-keto-PGF2 alpha (PG metabolite)], by radioenzymatic and radioimmunoassays, respectively, during and after recovery from AB. Blood was obtained from 15 infants during AB and from 14 and 9 of these infants when re-evaluated 6 and 18 months later, respectively. Mean (+/- 1 SEM) pre- and posttherapy (inhaled isoetharine) histamine levels (pg/ml), 1,923 +/- 980 and 1,035 +/- 250 during AB, respectively, were markedly higher than those of the same nonwheezing subjects at 18 months, 360 +/- 125, but unexpectedly lower than those at 6 months, 9,210 +/- 5,242. Of the 14 infants evaluated at 6 months, 7 had elevated histamine levels along with histories of recurrent wheezing after AB. Similarly, pre- and posttherapy PG metabolite levels (pg/ml), 1,033 +/- 419 and 1,613 +/- 527, respectively, were significantly higher than those of the same children when asymptomatic at 6 (27 +/- 7) and 18 months (68 +/- 25). Pre- and posttherapy levels of histamine and PG metabolite were higher than those of normal and sick, nonwheezing infants. These data indicate that histamine and PG metabolite are detectable in plasma during AB and suggest a role for histamine and PGF2 alpha in the pathogenesis of airways inflammation in AB.