The use of alcohol, tobacco, marihuana, cocaine, and bazuco was examined in a cross-sectional study of a random sample of 512 secondary-school students enrolled in public and private schools in Cali, Colombia. The overall prevalence of use for any of these substances was 59.38% in the public schools and 36.96% in the private schools (z = 4.6, P less than 0.05). The probability of finding an alcohol user was about 55.26%. The frequency of use for all the substances was 18.9% in the public schools and 7.46% in the private ones. Experience with marihuana, cocaine, and bazuco was more frequent in the public schools. The average age of users (19.91 years) was higher than that of non-users (16.25 years): t = 8.34, P less than 0.05. Students in the public schools with a family history of mental illness had almost a ninefold greater risk of being substance users (RR = 8.84, IC 95% = 1.22-3.37); among students in the private schools, having personal conflicts with authority figures (teachers and the police) was a significant risk factor (RR = 2.03, IC 95% = 1.22-3.37).