Little is known about the anti-asthmatic effects of powerful anti-inflammatory agents such as aspirin-like drugs. We compared the effects of two aspirin-like drugs with different pharmacologic activities, sodium salicylate (SSA) and indomethacin, with the effect of lysine acetylsalicylate (LASA), inhaled 30 min before challenge, on the early and the late asthmatic response induced by a single dose of allergen causing a 25% decrease in FEV1 in a preliminary challenge. Inhaled SSA partially prevented both the early and late response, providing a protection with respect to placebo of 22 +/- 6% in the early phase and 23 +/- 9% in the late phase of the response. These values were lower (but not significantly) than those of LASA (41 +/- 9% and 39 +/- 11%, respectively). In a second group of patients, indomethacin failed to affect the early response, while LASA provided a protection of 31 +/- 7%. However, these two drugs were equally effective in reducing the late response (44 +/- 18% and 39 +/- 17% protection for LASA and indomethacin, respectively). In subjects with an early response, despite being ineffective in preventing allergen-induced bronchoconstriction, indomethacin blocked the allergen-induced increase in bronchial hyperresponsiveness measured 2 h after challenge. We conclude that inhaled salicylates, but not indomethacin, exert a protective activity against the early allergic response. This difference is not explained by the different pattern of cyclooxygenase inhibitory activity of these drugs.