Aggregation tests were performed on platelet-rich plasma from healthy male volunteers to determine the minimum concentration of adenosine diphosphate (ADP), epinephrine, collagen, or thrombin required to induce secondary aggregation. Platelets were also analyzed for cholesterol and phospholipid, and in some cases their membrane fluidity was determined by fluorescence depolarization of the probe, diphenylhexatriene. Concentrations of the major lipoprotein fractions in the plasma were measured and related to the sensitivity of platelets to the four agonists. Low density lipoprotein (LDL) and total cholesterol concentrations, but not high density lipoproteins (HDL) or very low density lipoproteins (VLDL), were positively correlated with sensitivity to aggregation by epinephrine, but not by other agonists. By arrangement of the lipoprotein concentration into quintiles, the effect of LDL was most striking in the lower two quintiles, where the sensitivity to adrenaline and ADP were much diminished. The middle and upper two quintiles showed a similar sensitivity. Lower platelet cholesterol/phospholipid ratios were also associated with a reduced sensitivity to epinephrine or ADP, but only at the lower end of the range. Membrane microviscosity was correlated negatively with collagen sensitivity and with VLDL cholesterol concentrations, but positively with HDL cholesterol concentrations. Platelet behavior appears, therefore, to be influenced by lipoprotein concentrations within the range found in a healthy population.