Cyclic AMP and dibutyryl cyclic AMP as well as several 8-substituted analogs of cyclic AMP inhibited in vitro human blood neutrophil chemotaxis. Cyclic GMP enhanced chemotaxis. 8-substitution on the cyclic GMP nucleus markedly dampened the cyclic GMP effect. SQ 20,009, a potent phosphodiesterase inhibitor when tested alone inhibited chemotaxis; it potentiated the inhibition or enhancement of chemotaxis when combined with cyclic AMP or cyclic GMP, respectively.