Lower levels of plasma total cholesterol have been observed during severe infection, but it is not known whether the minor illnesses encountered in the general population are also associated with reduced cholesterol. This paper examines the relation between minor illness and plasma lipids, using 7- and 10-year follow-up data from more than 3,000 generally healthy participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. At both 7 and 10 years, approximately 8.5% of participants stated they had been "ill with cold, flu, fever, or vomiting in the past 24 hours." In both cross-sectional and longitudinal analyses, the plasma total cholesterol was about 5 mg/dl lower (p < 0.006) and high density lipoprotein cholesterol about 1.2 mg/dl lower (p < 0.12) in those who reported minor illness than in those who did not. Plasma triglycerides did not vary with minor illness. The authors conclude that reductions in plasma total, low density, and high density lipoprotein cholesterol mark an acute phase response even during minor illness. These reductions may bias surveys over a limited geographic area during a short period because the proportion with minor illness may vary locally. Because this effect should be stronger with more precise illness diagnosis, clinicians should avoid making measurements for cholesterol management when illness may alter plasma lipid levels and the resulting decisions.