This work demonstrated that batches of standard aqueous extracts could be prepared from single samples of cotton dust; green air-dried bract; or field dried bract. These dust or bract extracts were similar in total protein, total reducing sugar, hexoses, total lipid, histamine, and antigenic composition, permitting pooling of batches for use in cyclic adenosine 3', 5' monophosphate (cAMP) studies The effect of dust or bract extract pools on cAMP was tested in a model system using peripheral blood mononuclear leucocytes (MNL) from healthy volunteers. Crude cotton dust extract significantly elevated cAMP levels in MNL. This response was not due to stimulation of the beta-adrenergic or H(,2) receptor sites, nor to prostaglandin E(,1) generation by monocytes and/or platelets contaminating the MNL preparation Green bract extract, at 0.1 at 4.0 mg/ml significantly lowered basal cAMP levels in MNL. At a concentration of 0.2 mg/ml, this extract acted as a competitive antagonist of cAMP stimulation by isoproterenol over the range 1 x 10('-8) to 1 x 10('-4)M. However, when isoproterenol was increased to 1 x 10('-1)M and incubated with 0.2 mg/ml green bract extract, the cAMP response was significantly higher than with the same concentration of isoproterenol alone, suggesting a possible allosteric effect. Green bract, at 1.0 mg/ml, acted as a competitive antagonist appeared to be of molecular weight greater than 6,000; however, the possibility that low molecular weight compound(s) were complexed to these larger molecules could not be excluded Aqueous extract of field dried bract, at 0.1 to 5.0 mg/ml, did not affect basal cAMP levels. At concentrations from 0.1 to 5.0 mg/ml, this bract extract significantly antagonized cAMP stimulation by isoproterenol, in a competitive fashion The cAMP stimulatory action of cotton dust extract and ability of bract extracts to lower basal cAMP levels or act as antagonists of cAMP stimulation suggests a pharmacologic etiology. The pharmacologic action of these extracts could be responsible for bronchospasm, and/or mediator release in byssinotics. Thus, modulation of cAMP response by cotton components is proposed as a mechanism for byssinosis