This study was carried out to determine leukocyte phospholipase A2 (PLA2) activity and plasma lysophosphatidylcholine (LPC) levels in normal subjects and in patients with asthma and rhinitis and to examine their relationship to airway sensitivity to histamine. Leukocyte PLA2 activity and plasma LPC levels were highly correlated (rs = 0.90), and were found significantly raised in both the disease groups, more so in the asthmatics. Both PLA2 activity and LPC levels showed overall negative correlations with the log dose of histamine producing a 35% fall in specific airway conductance (PD35 histamine) when the patients and the normal subjects were examined together (rs = -0.77 and rs = -0.83, respectively). The patients with leukocyte PLA2 activity more than 1.8 U (nmol 14C-AA released/mg protein/10 min at 30 degrees C) or plasma LPC levels more than 8.7% of total phospholipids (mostly asthmatics) showed high airway sensitivity to histamine (PD35 histamine less than or equal to 1 mg/ml). On the other hand, the PD35 histamine values of patients with leukocyte PLA2 activity equal to or less than 1.96 U or plasma LPC levels equal to or less than 8.7% overlapped with those of normal subjects in the range of 1.2 to 10 mg/ml. Lowering of plasma LPC levels, which probably reflect tracheobronchial LPC content as shown in guinea pigs, seems to be an essential step in the return of airway reactivity toward normal.