STUDY OBJECTIVES: To analyse the relation between the longitudinal development of total serum cholesterol (TC), high density lipoprotein cholesterol (HDL), and the TC/ HDL ratio and the longitudinal development of the biological parameters body fatness (SSF), lean body mass (LBM), and cardiopulmonary fitness (VO2-max). The relations were analysed with generalised estimating equations (GEE). SETTING: The relations were investigated with data from the Amsterdam growth and health study, a longitudinal study in which six measurements were carried out within a period of 15 years. PARTICIPANTS: Altogether 98 females and 84 males aged 13 years at the start of the study. MAIN RESULTS: Adjusted for lifestyle and other biological parameters, the longitudinal development of TC was inversely related to the development of LBM (standardised regression coefficient beta = -0.27; p < or = 0.01) and positively to SSF (beta males = 0.32; p < or = 0.01 and beta females = 0.15; p < or = 0.01). HDL was inversely related to LBM (beta = -0.26; p < or = 0.01) and positively to VO2-max (beta = 0.08; p < or = 0.05). The TC/HDL ratio was positively related to SSF (beta males = 0.39; p < or = 0.01 and beta females = 0.13; p < or = 0.01) and inversely to VO2-max (beta = -0.09; p < or = 0.05). CONCLUSIONS: The longitudinal analyses showed that body fatness was related to a high risk profile with respect to hypercholesterolaemia, and cardiopulmonary fitness to a low risk profile. Furthermore, it was shown that using body mass index as an indicator of body fatness in relation to lipoprotein values, has some important drawbacks.