AbstractSea urchin spermatozoa react to transglutaminase inhibitors, which may antagonize the function of calmodulin, in dose‐dependent fashion. The optimum concentration of diallyl‐amino propionyl benzothiophenc (DAPBT), a potent, noncompetitive inhibitor of transglutaminase, 0.01 mM, causes a 3 1/2‐fold increase in the forward swimming speed of Arbacia sperm. This effect apparently involves calcium‐dependent enzymes since manipulation of both extracellular and intracellular calcium by means of chelating agents, calcium‐channel blockers, and calmodulin antagonists depresses the stimulatory effect of DAPBT. These results suggest that in the spermatozoa the interaction of flagellar sliding filaments may be mediated by reversible cross‐linking of the contractile proteins catalyzed by a calcium‐ dependent transglutaminase.