Collection of sensitive data with the use of video-enhanced, computer-assisted, self-administered interviews (V-CASI) has the potential to reduce interview bias and improve the validity of the study. The purpose of this study was to compare responses to sensitive questions elicited by V-CASI and by face-to-face interview (FTFI) methods. Women attending a New Orleans, Louisiana, public family planning or sexually transmitted disease clinic from July 1995 to July 1996, diagnosed with a Chlamydia trachomatis infection responded to eight close-ended behavioral questions (four socially undesirable, two socially desirable, and two neutral behaviors) using both FTFI and V-CASI techniques in a randomized crossover design. Of the 280 women included, the mean age was 23 years, 95 percent were African American, and 71 percent felt comfortable using computers. While kappa scores indicated good-to-excellent agreement between interview techniques, women tended to admit to socially undesirable behaviors more often on V-CASI compared with FTFI. Thirty percent of the women gave a discrepant response between V-CASI and FTFI toward social desirability. Women who reported a socially undesirable behavior in V-CASI (i.e., more than two sex partners and infrequent condom usage) were more likely to have a discrepant response. Utilization of the same logistic regression model to predict condom use yielded different results when data from V-CASI were used compared with data from FTFI. The V-CASI technique can reduce social desirability bias and improve validity in research requiring information on sensitive sexual behaviors. Am J Epidemiol 1999; 149:950–4.