The purpose of this study was to identify compounds that could potentially be useful for vas irrigation at the time of vasectomy. We studied the in vitro effects of a group of membrane-active and ion-channel blocking agents on human sperm motility, viability and cervical mucus penetration. Diltiazem, an anti-arrhythmic drug, and methylene blue, an agent commonly used in vasography, showed the most promising effects with marked reduction of sperm motility and cervical mucus penetration after incubation with sperm for a short period of 15 min. Diltiazem was more effective than methylene blue in inhibiting the motility and viability of sperm. Furthermore, unlike methylene blue, diltiazem significantly compromised sperm viability. Other compounds studied, such as lidocaine, nicardipine and Neosporin((R)), showed only partial inhibitory activity. Based on the data reported herein, both diltiazem and methylene blue appear to be suitable candidates to be developed for vas irrigation at the time of vasectomy.