Two cyclic AMP-binding proteins, not identical with regulatory subunits of protein kinases, have been isolated from Trypanosoma gambiense. The cyclic AMP receptors were separated by gel chromatography on the basis of their molecular weights. The binding constants of the high and the low molecular weight receptors for cyclic AMP were determined to be 0.4 muM and 0.6 muM, respectively. Cyclic IMP and cyclic GMP compete with cyclic AMP for the binding sites of both receptors. The cyclic AMP binding of the low molecular weight receptor was competitively inhibitied by adenine derivatives. The binding capacity of the high molecular weight receptor was enhanced about two-fold by proteolytic modification with trypsin.