Sodium cellulose sulfate (CS) is under development as a vaginal microbicide and spermicide. This was a Phase I, randomized, double-blind study of men to assess acceptability, safety, and degree of penile irritation of seven consecutive daily doses of CS compared to an active control containing nonoxynol-9 (Conceptrol). The data suggest that CS gel is not more irritating to the male genitalia than Conceptrol. This, along with the minimal irritation seen in a Phase I safety study in women following 6 consecutive days of vaginal administration, suggests that CS could be used in future studies, without undue risk, where couples engage in vaginal intercourse. Male volunteers in future studies should be informed that 1 out of 24 participants in the CS group in this study experienced tingling and slight stinging for a brief time after exposure compared with 3 out of 12 in the Conceptrol group who reported similar symptoms.