KS-619-1, a new inhibitor of Ca²⁺ and calmodulin-dependent cyclic nucleotide phosphodiesterase, was isolated from the cultured broth of Streptomyces californicus. KS-619-1 has an anthraquinone moiety. IC₅₀ values for the effect of KS-619-1 on Ca²⁺ and calmodulin-stimulated activity of bovine brain and heart enzymes were 2.0 and 1.5 μM, respectively. On the other hand, basal activity (the activity in the presence of ethylene bis(oxyethylenenitrilo)-tetraacetic acid (EOTA) instead of Ca²⁺/calmodulin) of the bovine brain enzyme, calmodulin-independent cyclic nucleotide phosphodiesterase from bovine heart, and protein kinase C from rat brain were inhibited by KS-619-1 to a lesser extent with IC₅₀ values; 12.3, 25.9 and 151 μM, respectively.