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Many research participants are misinformed about research terms, procedures, and goals; however, no validated instruments exist to assess individual’s comprehension of health-related research information. We propose research literacy as a concept that incorporates understanding about the purpose and nature of research.We developed the Research and Knowledge Scale (RaKS) to measure research literacy in a culturally, literacy-sensitive manner. We describe its development and psychometric properties.Qualitative methods were used to assess perspectives of research participants and researchers. Literature and informed consent reviews were conducted to develop initial items. These data were used to develop initial domains and items of the RaKS, and expert panel reviews and cognitive pretesting were done to refine the scale. We conducted psychometric analyses to evaluate the scale.The cross-sectional survey was administered to a purposive community-based sample (n=430) using a Web-based data collection system and paper.We did classic theory testing on individual items and assessed test-retest reliability and Kuder-Richardson-20 for internal consistency. We conducted exploratory factor analysis and analysis of variance to assess differences in mean research literacy scores in sociodemographic subgroups.The RaKS is comprised of 16 items, with a Kuder-Richardson-20 estimate of 0.81 and test-retest reliability 0.84. There were differences in mean scale scores by race/ethnicity, age, education, income, and health literacy (all P<0.01).This study provides preliminary evidence for the reliability and validity of the RaKS. This scale can be used to measure research participants’ understanding about health-related research processes and identify areas to improve informed decision-making about research participation.