A variety of drugs from different pharmacologic classes were tested for their effects on the motility of human spermatozoa. Most of the compounds tested inhibited sperm motility and a common mechanism of action for many of these agents was indicated by the observation that their inhibitory potency could be reduced by adenylic acid. From structure-activity relationships, the effect of these local anesthetic-like compounds on the fluorescence of the membrane probe-1-anilinonapthalene sulfonate (ANS), and their effects on metabolism, a mechanism of action, based on the bilayer couple hypothesis of drug-membrane interaction (Sheetz and Singer, 1974) is suggested.