It has been previously shown that inhaled cotton bract tannin induces an acute pulmonary inflammatory response that includes the release of arachidonic acid (C20:4) metabolites. Here it is shown that tannin causes the accumulation of free fatly acids from rabbit resident alveolar macrophages by inhibiting their reincorporation into membrane phospholipids. Using saturated and unsaturated fatty acids, it was shown that after 30 minutes of stimulation with tannin, incorporation was decreased for all fatty acids studied. The inhibitory effect of tannin on C20:4 incorporation could be detected with as little as 5 minutes exposure to tannin. When alveolar macrophages were pulsed with tannin for 30 minutes and then exposed to exogenous C20:4, the inhibitory effect of tannin on C20:4 incorporation could be seen as soon as 15 minutes after the addition of C20:4. Longer time periods were required before inhibition of other fatty acids became significant. These data suggest the mechanism of tannin-mediated inhibition of C20:4 incorporation may differ from that for other fatty acids. Since C20:4 is the precursor of several important inflammatory molecules, the inhibition of its reacylation into membrane phospholipids may partially account for the pro-inflammatory effect of tannin.