BACKGROUND Many studies measure sex behavior to determine the efficacy of sexually transmitted disease (STD)/HIV prevention interventions. GOAL To determine how well measured behavior reflects STD incidence. STUDY DESIGN Data from a trial (Project RESPECT) were analyzed to compare behavior and incidence of STD (gonorrhea, chlamydia, syphilis, HIV) during two 6-month intervals. RESULTS A total of 2879 persons had 5062 six-monthly STD exams and interviews; 8.9% had a new STD in 6 months. Incidence was associated with demographic factors but only slightly associated with number of partners and number of unprotected sex acts with occasional partners. Many behaviors had paradoxical associations with STD incidence. After combining behavior variables to compare persons with highest and lowest risk behaviors, the STD incidence ratio was only 1.7. CONCLUSION Behavioral interventions have prevented STD. We found people tend to have safe sex with risky partners and risky sex with safe partners. Therefore, it is difficult to extrapolate the disease prevention efficacy of an intervention from a measured effect on behavior alone.