To assess relationships between pediatric lipids and subsequent cardiovascular disease (CVD) in the fourth to fifth decades, we conducted 22- to 31-year follow-up studies (1998-2003) in former schoolchildren first studied in 1973-1976. The follow-up included 53% of eligible former subjects. We compared pediatric and adult body mass (in kilograms per square meter) and lipids in 19 cases with at least 1 CVD event and in 789 CVD event-free subjects. Mean +/- SD age was 12.3 +/- 3.3 years at entry and 38.5 +/- 3.8 years at follow-up. Mean age at the first CVD event was 37.1 +/- 4.9 years. The major novel finding of our study was that childhood triglycerides (TG) were consistently and independently associated with young adult CVD. The distributions of both childhood and adult TG were shifted to higher levels in the cases than controls. Of the 19 cases, 7 (37%) had childhood TG greater than the pediatric 95th percentile (153 mg/dL); and 6 of these 7 had high TG (>/=150 mg/dL) at adult follow-up. Overall, 61% of cases had high TG as adults. After adjusting for age, sex, and race, by analysis of variance, cases had higher TG levels both in childhood and in young adulthood. A bootstrapping method and the Cox proportional hazard analysis were used to predict CVD in the cohort with explanatory variables sex; race; childhood body mass index, low-density lipoprotein, log high-density lipoprotein cholesterol, and log TG; and adult cigarette smoking and type 2 diabetes mellitus. Childhood TG level was a significant, independent explanatory variable for young adult CVD hazard (hazard ratio, 5.35; 95% confidence interval, 1.69-20.0 for each 1-unit increase in natural logarithm scale) along with adult type 2 diabetes mellitus (hazard ratio, 19.4; 95% confidence interval, 4.24-114.2). Pediatric hypertriglyceridemia appears to be a significant, independent, potentially reversible correlate of young adult CVD.