The current study was conducted to determine if smokers and nonsmokers differ in serum concentrations of high-density lipoprotein cholesterol (HDL-C) before smoking initiation and if a decline in HDL-C levels could be detected among adolescents during the first two years of smoking. Changes in HDL-C levels and smoking were observed longitudinally in 1983, 1984, and 1985 among 691 seventh and eighth graders (age range, 12 to 14 years) from two German cities; 82% were nonsmokers at baseline. For these baseline nonsmokers, no differences in baseline HDL-C concentrations were found between those who became smokers and those who remained nonsmokers. In contrast, those who became light (one to 39 cigarettes per week) or moderate (greater than or equal to 40 cigarettes per week) smokers by one or two years after the initial examination evidenced lower mean HDL-C concentrations relative to persistent nonsmokers at follow-up, constituting a decrement of -0.016 mmol/L [SE = .035] (-0.6 mg/dL) [SE = 1.4] for light smokers and -0.114 mmol/L [SE = .064] (-4.4 mg/dL) [SE = 2.5] for moderate smokers. These findings suggest that short-term exposure to cigarette smoke at low levels may have atherogenic consequences.