This analysis examined the importance of differential exposure to infected partners in epidemiologic studies of latex condom effectiveness for prevention of sexually transmitted infections. Cross-sectional, enrollment visit data were analyzed from Project RESPECT, a trial of counseling interventions conducted at five publicly funded US sexually transmitted disease clinics between 1993 and 1997. The association between consistent condom use in the previous 3 months and prevalent gonorrhea and chlamydia (Gc/Ct) was compared between participants known to have infected partners and participants whose partner infection status was unknown. Among 429 participants with known Gc/Ct exposure, consistent condom use was associated with a significant reduction in prevalent gonorrhea and chlamydia. Among 4,314 participants with unknown Gc/Ct exposure, consistent condom use was associated with a lower reduction in prevalent gonorrhea and chlamydia