A case-control study was done to evaluate the effectiveness of vaginal spermicides as a prophylaxis against gonorrhea. The subjects included 735 women with gonorrhea and 958 controls seen in a sexually transmitted disease clinic. The relative risk (RR) of gonorrhea for spermicide users compared with nonusers was 0.67 with 90% confidence limits, 0.44 to 1.0. This RR was 0.47 (90% confidence limits, 0.25 to 0.87) after the exclusion of women using oral contraceptives, an intrauterine device, or with a tubal ligation. The protective effect of spermicides was confined largely to women who had also used diaphragms or whose partners had used condoms. The RR of gonorrhea for spermicide and condom users relative to nonusers of spermicides, condoms, and diaphragms was 0.41 (90% confidence limits, 0.21 to 0.79), while for spermicide and diaphragm users, this RR was 0.45 (90% confidence limits, 0.15 to 1.3). These results suggest that a woman can appreciably decrease her risk of contracting gonorrhea if she uses spermicides in conjunction with either the diaphragm or the condom.