Aqueous cotton dust extracts (ACDE) stimulated production of cyclic adenosine monophosphate (cAMP) in normal human peripheral blood mononuclear leucocytes (MNL). This response was not due to prostaglandin production by monocytes or platelets in the cell preparation nor to stimulation of the beta-adrenergic or H2 receptors; however, desensitization experiments indicated that the response may be receptor mediated. The possible involvement of such receptor desensitization in byssinosis pathogenesis is discussed.