In Dictyostelium discoideumamoebae, binding of cyclic AMP (cAMP) to surface receptors elicits numerous responses including chemotaxis, cyclic GMP (cGMP) accumulation, and activation of adenylate cyclase. The specificity of the surface cAMP receptor which mediates activation of adenylate cyclase and cAMP secretion was determined by testing the relative effectiveness of a series of 10 cAMP analogs. Each of the 10 analogs elicited cAMP secretion, chemotaxis, and cGMP accumulation in the same dose range. The order of potency for eliciting these responses (cAMP > 2′-H-cAMP >N1-O-cAMP > cAMPS(Sp) > 6-Cl-cAMP > cAMPN(CH3)2(Sp) > 3′-NH-cAMP > 8-Br-cAMP > cAMPS(Rp) > cAMPN(CH3)2(Rp)) matches that for binding to the major cell surface cAMP binding sites and differs from that of the cell surface phosphodiesterase and the major intracellular cAMP binding protein. © 1986.