The reaction of the 5'-AMP with water soluble carbodiimide (EDAC) in the presence of Na+-montmorillonite 22A results in the formation of 2',5'-(pA)2 (18.9%), 3',5'-(pA)2 (11%), and AppA (4.8%). When poly(U) is used in place of the clay the product yields are 2',5'-(pA)2 (15.5%), 3',5'-(pA)2 (3.7%) and AppA (14.9%). The 3',5'-cyclic dinucleotide, 3',5'-c(pA)2, is also formed when poly(U) is used. AppA is the principal reaction product when neither clay nor poly(U) is present in the reaction mixture. Products which contain the phosphodiester bond are formed at different ionic strengths, pH and temperatures using Na+-montmorillonite. Phosphodiester bond formation was not observed when Cu2+-montmorillonite was used or when DISN was used in the place of EDAC. The extent catalysis of phosphodiester bond formation varied with the particular clay mineral used. Those Na+-clays which bind 5'-AMP more strongly are better catalysts. Cu2+-montmorillonite, which binds 5'-AMP strongly, exhibits no catalytic activity.