Positive school climates and student drug testing have been separately proposed as strategies to reduce student substance use in high schools. However, the effects of drug testing programs may depend on the favorability of school climates. This study examined the association between school drug testing programs and student substance use in schools with different climates. The analysis was based on a nationally representative sample of 943 high school students (48 percent female) ranging from 14 to 19 years of age (62 percent identifying as white, 18 percent Hispanic, 13 percent African-American, and 7 percent in other categories). Results showed that both male and female students in schools with positive climates reported lower levels of personal substance use. Drug testing was associated with lower levels of personal substance use in positive school climates, but only for female students. There was no relationship between drug testing and male students' substance use. The results are discussed in terms of the importance of considering school climates before implementing drug-testing programs in high schools. (Published Abstract)