The effects of lincomycin and clindamycin on neuromuscular transmission in vitro were studied. Standard microelectrode technics were used to measure miniature endplate potential (MEPP) amplitude and frequency, and endplate sensitivity to acetycholine on the frog sartorius muscle. Twitch tension and nerve terminal acetycholine release were also studied. In the drug concentration range where twitch tension changes occurred, both drugs caused marked decreases in MEPP amplitude and decreases in endplate sensitivity to iontophoretically applied acetylcholine. Lincomycin did not alter MEPP frequency but decreased acetylcholine release. Clindamycin increased MEPP frequency and increased acetylcholine release. The study shows that both lincomycin and clindamycin cause blockade of neuromuscular transmission through a postsynaptic action. However, at high concentrations, lincomycin has a nerve-terminal depressant effect, while clindamycin has a marked presynaptic stimulatory effect.